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NeuroMolecular Medicine

, Volume 20, Issue 1, pp 18–36 | Cite as

Molecular Insights into the Roles of Rab Proteins in Intracellular Dynamics and Neurodegenerative Diseases

  • Shobi Veleri
  • Pradeep Punnakkal
  • Gary L. Dunbar
  • Panchanan Maiti
Review Paper

Abstract

In eukaryotes, the cellular functions are segregated to membrane-bound organelles. This inherently requires sorting of metabolites to membrane-limited locations. Sorting the metabolites from ribosomes to various organelles along the intracellular trafficking pathways involves several integral cellular processes, including an energy-dependent step, in which the sorting of metabolites between organelles is catalyzed by membrane-anchoring protein Rab-GTPases (Rab). They contribute to relaying the switching of the secretory proteins between hydrophobic and hydrophilic environments. The intracellular trafficking routes include exocytic and endocytic pathways. In these pathways, numerous Rab-GTPases are participating in discrete shuttling of cargoes. Long-distance trafficking of cargoes is essential for neuronal functions, and Rabs are critical for these functions, including the transport of membranes and essential proteins for the development of axons and neurites. Rabs are also the key players in exocytosis of neurotransmitters and recycling of neurotransmitter receptors. Thus, Rabs are critical for maintaining neuronal communication, as well as for normal cellular physiology. Therefore, cellular defects of Rab components involved in neural functions, which severely affect normal brain functions, can produce neurological complications, including several neurodegenerative diseases. In this review, we provide a comprehensive overview of the current understanding of the molecular signaling pathways of Rab proteins and the impact of their defects on different neurodegenerative diseases. The insights gathered into the dynamics of Rabs that are described in this review provide new avenues for developing effective treatments for neurodegenerative diseases-associated with Rab defects.

Keywords

Membrane anchoring Rab proteins Molecular switches Synaptic vesicles Exocytosis Neurodegeneration 

Abbreviations

α-Syn

Alpha-synuclein

AD

Alzheimer’s disease

Amyloid beta protein

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

APP

Amyloid precursor proteins

APPL

Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper

BBSome

Bardet–Biedl syndrome

BDNF

Brain-derived neurotropic factor

CAG

Triplet nucleotide codes for glutamine

CCV

Clathrin-coated vesicles

CMTB

Charcot–Marie–Tooth-type 2B

CRD

Cone-rod dystrophy

CR

Carpenter syndrome

DA

Dopamine

DENN

Differentially expressed in normal and neoplastic cells

EE

Early endosomes

EEA1

Early endosome adapter1

EAAC1

Glutamate/cysteine transporter

ER

Endoplasmic reticulum

GAP

GTP hydrolysis activator protein

GC

Golgi complex

GDP

Guanosine diphosphate

GEF

Guanine nucleotide exchange factor

GLUT

Glucose transporter

GTP

Guanosine triphosphate

GS

Griscelli syndrome

GSH

Glutathione

HD

Huntington’s disease

Hh

Hedgehog

HTT

Huntingtin protein

IFT

Intraflagellar transport

LBD

Lewy body disease

LE

Late endosome

LRRK

Leucine-rich repeat kinase 2

LTP

Long-term potentiation

LTD

Long-term depression

MAM

Mitochondria-associated membranes

mHTT

Mutant Huntingtin protein

MS

Martsolf syndrome

MSN

Medium spiny neurons

NMDA

N-acetyl d-aspartate

NMDAR

N-acetyl d-aspartate receptor

NSF

N-ethylmaleimide-sensitive factor

PD

Parkinson’s disease

polyQ

Polyglutamine

PSEN-1

Presenilin-1

Rab-GDI

Rab-interacting protein GDP-dissociation inhibitor

REP

Rab escort protein

RPE

Retinal pigment epithelium

Rab

Ras genes from rat brain

RBP3A

Rab3A effector Rabphilin-3A

RE

Recycling endosome

SNpc

Substantia nigra pars compacta

SV

Synaptic vesicle

TGN

Trans-Golgi network

TMEM230

Transmembrane protein 230

TrkB

Tyrosine kinase-B

t-SNARE

Target-soluble NSF attachment protein receptor

VAMP

Vesicle associated membrane protein

v-SNARE

Vesicle-soluble NSF attachment protein receptor

WMS

Warburg-microsyndrome

Ypt

Yeast-related protein

Notes

Acknowledgements

S.V. acknowledges the support of Dr. A. Ajayaghosh, Director, CSIR-NIIST, during the preparation of this manuscript. Ms. Swapna U Sasi is acknowledged for help on initial version of the manuscript.

Author’s Contributions

S.V. conceived the review and the figures. P.M. contributed on neurodegenerative diseases and edited the manuscript. P.P. contributed the neurotransmitter receptors part and edited the manuscript. G.L.D. helped edit the later drafts of the manuscripts.

Funding

S.V. and P.P. acknowledge Department of Biotechnology, Ministry of Science and Technology, Government of India for financial supports as DBT-Ramalingaswami Re-entry Fellows: S.V.: SAN No.102/IFD/SAN/351/2016-14 dated May 5, 2016; and P.P: No. BT/RLF/Re-entry/04/2012. PP is also supported by DBT grant No. BT/PR10968/MED/30/1326/2014.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Ali, B. R., et al. (2004). Multiple regions contribute to membrane targeting of Rab GTPases. Journal of Cell Science, 117(Pt 26), 6401–6412.PubMedCrossRefGoogle Scholar
  2. Aligianis, I. A., et al. (2005). Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. Nature Genetics, 37(3), 221–223.PubMedCrossRefGoogle Scholar
  3. Aloisi, A. L., & Bucci, C. (2013). Rab GTPases-cargo direct interactions: Fine modulators of intracellular trafficking. Histology and Histopathology, 28(7), 839–849.PubMedGoogle Scholar
  4. Ang, A. L., et al. (2003). The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells. Journal of Cell Biology, 163(2), 339–350.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Arimura, N., et al. (2009). Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Developmental Cell, 16(5), 675–686.PubMedCrossRefGoogle Scholar
  6. Armstrong, A., et al. (2014). Lysosomal network proteins as potential novel CSF biomarkers for Alzheimer’s disease. NeuroMolecular Medicine, 16(1), 150–160.PubMedCrossRefGoogle Scholar
  7. Arriagada, C., et al. (2007). Endosomal abnormalities related to amyloid precursor protein in cholesterol treated cerebral cortex neuronal cells derived from trisomy 16 mice, an animal model of Down syndrome. Neuroscience Letters, 423(2), 172–177.PubMedCrossRefGoogle Scholar
  8. Arriagada, C., et al. (2010). Apoptosis is directly related to intracellular amyloid accumulation in a cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down syndrome. Neuroscience Letters, 470(1), 81–85.PubMedCrossRefGoogle Scholar
  9. Babbey, C. M., Bacallao, R. L., & Dunn, K. W. (2010). Rab10 associates with primary cilia and the exocyst complex in renal epithelial cells. American Journal of Physiology-Renal Physiology, 299(3), F495–F506.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Baldini, G., et al. (1992). Cloning of a Rab3 isotype predominantly expressed in adipocytes. Proceedings of the National Academy of Sciences, 89(11), 5049–5052.CrossRefGoogle Scholar
  11. Barr, F. A. (2013). Review series: Rab GTPases and membrane identity: causal or inconsequential? J Cell Biology, 202(2), 191–199.CrossRefGoogle Scholar
  12. Binotti, B., Jahn, R., & Chua, J. J. (2016). Functions of rab proteins at presynaptic sites. Cells, 5(1), 7.PubMedCentralCrossRefGoogle Scholar
  13. Binotti, B., et al. (2015). The GTPase Rab26 links synaptic vesicles to the autophagy pathway. Elife, 4, e05597.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Blumer, J., et al. (2013). RabGEFs are a major determinant for specific Rab membrane targeting. J Cell Biology., 200(3), 287–300.CrossRefGoogle Scholar
  15. Bonifacino, J. S., & Glick, B. S. (2004). The mechanisms of vesicle budding and fusion. Cell, 116(2), 153–166.PubMedCrossRefGoogle Scholar
  16. Brown, T. C., et al. (2005). NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron, 45(1), 81–94.PubMedCrossRefGoogle Scholar
  17. Brown, T. C., et al. (2007). Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation. Journal of Neuroscience, 27(48), 13311–13315.PubMedCrossRefGoogle Scholar
  18. Bucci, C., Alifano, P., & Cogli, L. (2014). The role of rab proteins in neuronal cells and in the trafficking of neurotrophin receptors. Membranes (Basel)., 4(4), 642–677.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bucci, C., & Chiariello, M. (2006). Signal transduction gRABs attention. Cellular Signalling, 18(1), 1–8.PubMedCrossRefGoogle Scholar
  20. Bui, M., et al. (2010). Rab32 modulates apoptosis onset and mitochondria-associated membrane (MAM) properties. Journal of Biological Chemistry, 285(41), 31590–31602.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Carpenter, G. (1909). Acrocephaly, with other congenital malformations. Proc R Soc Med, 2(Sect Study Dis Child), 45–53.PubMedPubMedCentralGoogle Scholar
  22. Casey, P. J., & Seabra, M. C. (1996). Protein prenyltransferases. Journal of Biological Chemistry, 271(10), 5289–5292.PubMedCrossRefGoogle Scholar
  23. Castillo, P. E., et al. (1997). Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature, 388(6642), 590–593.PubMedCrossRefGoogle Scholar
  24. Chavrier, P., et al. (1990). Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell, 62(2), 317–329.PubMedCrossRefGoogle Scholar
  25. Chavrier, P., et al. (1991). Hypervariable C-terminal domain of rab proteins acts as a targeting signal. Nature, 353(6346), 769–772.PubMedCrossRefGoogle Scholar
  26. Chen, W., et al. (1998). Rab11 is required for trans-golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor. Molecular Biology of the Cell, 9(11), 3241–3257.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Coleman, W. L., Bill, C. A., & Bykhovskaia, M. (2007). Rab3a deletion reduces vesicle docking and transmitter release at the mouse diaphragm synapse. Neuroscience, 148(1), 1–6.PubMedCrossRefGoogle Scholar
  28. Coppola, T., et al. (2001). Direct interaction of the Rab3 effector RIM with Ca2 + channels, SNAP-25, and synaptotagmin. Journal of Biological Chemistry, 276(35), 32756–32762.PubMedCrossRefGoogle Scholar
  29. Dalfo, E., et al. (2004). Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease. Neurobiology of Diseases, 16(1), 92–97.CrossRefGoogle Scholar
  30. de Renzis, S., Sonnichsen, B., & Zerial, M. (2002). Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes. Nature Cell Biology, 4(2), 124–133.PubMedCrossRefGoogle Scholar
  31. Deak, F., et al. (2006). Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion. EMBO Journal, 25(12), 2856–2866.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Deretic, D., & Papermaster, D. S. (1993). Rab6 is associated with a compartment that transports rhodopsin from the trans-Golgi to the site of rod outer segment disk formation in frog retinal photoreceptors. Journal of Cell Science, 106(Pt 3), 803–813.PubMedGoogle Scholar
  33. Deretic, D., et al. (1995). rab8 in retinal photoreceptors may participate in rhodopsin transport and in rod outer segment disk morphogenesis. Journal of Cell Science, 108(Pt 1), 215–224.PubMedGoogle Scholar
  34. Di Giovanni, S., et al. (2006). The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO Journal, 25(17), 4084–4096.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Di Paolo, G., & De Camilli, P. (2006). Phosphoinositides in cell regulation and membrane dynamics. Nature, 443(7112), 651–657.PubMedCrossRefGoogle Scholar
  36. Diekmann, Y., et al. (2011). Thousands of rab GTPases for the cell biologist. PLoS Computational Biology, 7(10), e1002217.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Echard, A., et al. (1998). Interaction of a Golgi-associated kinesin-like protein with Rab6. Science, 279(5350), 580–585.PubMedCrossRefGoogle Scholar
  38. Eggenschwiler, J. T., et al. (2006). Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Development Biology, 290(1), 1–12.CrossRefGoogle Scholar
  39. Elias, M., et al. (2012). Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases. Journal of Cell Science, 125(Pt 10), 2500–2508.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fortin, D. L., et al. (2004). Lipid rafts mediate the synaptic localization of alpha-synuclein. Journal of Neuroscience, 24(30), 6715–6723.PubMedCrossRefGoogle Scholar
  41. Fukuda, M. (2003). Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2. Journal of Biological Chemistry, 278(17), 15373–15380.PubMedCrossRefGoogle Scholar
  42. Furusawa, K., et al. (2017). Cdk5 Regulation of the GRAB-Mediated Rab8–Rab11 Cascade in Axon Outgrowth. Journal of Neuroscience, 37(4), 790–806.PubMedCrossRefGoogle Scholar
  43. Gallwitz, D., Donath, C., & Sander, C. (1983). A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product. Nature, 306(5944), 704–707.PubMedCrossRefGoogle Scholar
  44. Gerges, N. Z., Backos, D. S., & Esteban, J. A. (2004). Local control of AMPA receptor trafficking at the postsynaptic terminal by a small GTPase of the Rab family. Journal of Biological Chemistry, 279(42), 43870–43878.PubMedCrossRefGoogle Scholar
  45. Gerondopoulos, A., et al. (2012). BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Current Biology, 22(22), 2135–2139.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Ghavami, S., et al. (2014). Autophagy and apoptosis dysfunction in neurodegenerative disorders. Progress in Neurobiology, 112, 24–49.PubMedCrossRefGoogle Scholar
  47. Giannandrea, M., et al. (2010). Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. The American Journal of Human Genetics, 86(2), 185–195.PubMedCrossRefGoogle Scholar
  48. Goldenring, J. R., et al. (1996). Rab11 is an apically located small GTP-binding protein in epithelial tissues. American Journal of Physiology, 270(3 Pt 1), G515–G525.PubMedGoogle Scholar
  49. Goody, R. S., Rak, A., & Alexandrov, K. (2005). The structural and mechanistic basis for recycling of Rab proteins between membrane compartments. Cellular and Molecular Life Sciences, 62(15), 1657–1670.PubMedCrossRefGoogle Scholar
  50. Griscelli, C., & Prunieras, M. (1978). Pigment dilution and immunodeficiency: A new syndrome. International Journal of Dermatology, 17(10), 788–791.PubMedCrossRefGoogle Scholar
  51. Gurkan, C., et al. (2005). Large-scale profiling of Rab GTPase trafficking networks: The membrome. Molecular Biology of the Cell, 16(8), 3847–3864.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Han, C., et al. (2016). Epileptic encephalopathy caused by mutations in the guanine nucleotide exchange factor DENND5A. The American Journal of Human Genetics, 99(6), 1359–1367.PubMedCrossRefGoogle Scholar
  53. Handley, M. T., et al. (2013). Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. Human Mutation, 34(5), 686–696.PubMedCrossRefGoogle Scholar
  54. Huber, L. A., et al. (1993). Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p. Journal of Cell Biology, 123(1), 47–55.PubMedCrossRefGoogle Scholar
  55. Hutagalung, A. H., & Novick, P. J. (2011). Role of Rab GTPases in membrane traffic and cell physiology. Physiology Review, 91(1), 119–149.CrossRefGoogle Scholar
  56. Imarisio, S., et al. (2008). Huntington’s disease: From pathology and genetics to potential therapies. Biochemical Journal, 412(2), 191–209.PubMedCrossRefGoogle Scholar
  57. Jahn, R., & Scheller, R. H. (2006). SNAREs–engines for membrane fusion. Nature Reviews Molecular Cell Biology, 7(9), 631–643.PubMedCrossRefGoogle Scholar
  58. Jenkins, D., et al. (2007). RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. American Journal of Human Genetics, 80(6), 1162–1170.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Jensen, V. L., et al. (2016). Whole-organism developmental expression profiling identifies RAB-28 as a novel ciliary GTPase associated with the BBSome and intraflagellar transport. PLoS Genetics, 12(12), e1006469.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Jeong, K., et al. (2012). Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of caveolin-2 in response to insulin. Traffic., 13(9), 1218–1233.PubMedCrossRefGoogle Scholar
  61. Jordens, I., et al. (2001). The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Current Biology, 11(21), 1680–1685.PubMedCrossRefGoogle Scholar
  62. Kawauchi, T., et al. (2010). Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking. Neuron, 67(4), 588–602.PubMedCrossRefGoogle Scholar
  63. Klein, C., et al. (1994). Partial albinism with immunodeficiency (Griscelli syndrome). Journal of Pediatrics, 125(6 Pt 1), 886–895.PubMedCrossRefGoogle Scholar
  64. Knodler, A., et al. (2010). Coordination of Rab8 and Rab11 in primary ciliogenesis. Proceedings of the National Academy of Sciences, 107(14), 6346–6351.CrossRefGoogle Scholar
  65. Kontopoulos, E., Parvin, J. D., & Feany, M. B. (2006). Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Human Molecular Genetics, 15(20), 3012–3023.PubMedCrossRefGoogle Scholar
  66. Kubo, S., et al. (2005). A combinatorial code for the interaction of alpha-synuclein with membranes. Journal of Biological Chemistry, 280(36), 31664–31672.PubMedCrossRefGoogle Scholar
  67. Lane, K. T., & Beese, L. S. (2006). Thematic review series: Lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. Journal of Lipid Research, 47(4), 681–699.PubMedCrossRefGoogle Scholar
  68. Lanzetti, L., et al. (2000). The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature, 408(6810), 374–377.PubMedCrossRefGoogle Scholar
  69. Larijani, B., et al. (2003). Multiple factors contribute to inefficient prenylation of Rab27a in Rab prenylation diseases. Journal of Biological Chemistry, 278(47), 46798–46804.PubMedCrossRefGoogle Scholar
  70. Lee, H. J., Patel, S., & Lee, S. J. (2005). Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. Journal of Neuroscience, 25(25), 6016–6024.PubMedCrossRefGoogle Scholar
  71. Lee, G. I., et al. (2017). A novel likely pathogenic variant in the RAB28 gene in a Korean patient with cone-rod dystrophy. Ophthalmic Genetics, 38(6), 587–589.PubMedCrossRefGoogle Scholar
  72. Leung, K. F., Baron, R., & Seabra, M. C. (2006). Thematic review series: Lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. Journal of Lipid Research, 47(3), 467–475.PubMedCrossRefGoogle Scholar
  73. Li, X., & DiFiglia, M. (2012). The recycling endosome and its role in neurological disorders. Progress in Neurobiology, 97(2), 127–141.PubMedCrossRefGoogle Scholar
  74. Li, G., & Stahl, P. D. (1993). Structure-function relationship of the small GTPase rab5. Journal of Biological Chemistry, 268(32), 24475–24480.PubMedGoogle Scholar
  75. Li, X., et al. (2008). A function of huntingtin in guanine nucleotide exchange on Rab11. NeuroReport, 19(16), 1643–1647.PubMedCrossRefGoogle Scholar
  76. Li, X., et al. (2009). Disruption of Rab11 activity in a knock-in mouse model of Huntington’s disease. Neurobiology of Diseases, 36(2), 374–383.CrossRefGoogle Scholar
  77. Lim, Y. S., Chua, C. E., & Tang, B. L. (2011). Rabs and other small GTPases in ciliary transport. Biol ogy of the Cell, 103(5), 209–221.CrossRefGoogle Scholar
  78. Lim, Y. S., & Tang, B. L. (2015). A role for Rab23 in the trafficking of Kif17 to the primary cilium. Journal of Cell Science, 128(16), 2996–3008.PubMedCrossRefGoogle Scholar
  79. Maiti, P., et al., Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin. Biomed Res Int. 2014: p. 495091.Google Scholar
  80. Mallard, F., et al. (2002). Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. Journal of Cell Biology, 156(4), 653–664.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Maltese, W. A. (1990). Posttranslational modification of proteins by isoprenoids in mammalian cells. FASEB J, 4(15), 3319–3328.PubMedCrossRefGoogle Scholar
  82. Martinez, O., & Goud, B. (1998). Rab proteins. Biochimica et Biophysica Acta, 1404(1–2), 101–112.PubMedCrossRefGoogle Scholar
  83. Martinez, O., et al. (1994). The small GTP-binding protein rab6 functions in intra-Golgi transport. Journal of Cell Biology, 127(6 Pt 1), 1575–1588.PubMedCrossRefGoogle Scholar
  84. Matsui, Y., et al. (1988). Nucleotide and deduced amino acid sequences of a GTP-binding protein family with molecular weights of 25,000 from bovine brain. Journal of Biological Chemistry, 263(23), 11071–11074.PubMedGoogle Scholar
  85. McCaffrey, M. W., et al. (2001). Rab4 affects both recycling and degradative endosomal trafficking. FEBS Letters, 495(1–2), 21–30.PubMedCrossRefGoogle Scholar
  86. Meggouh, F., et al. (2006). Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene. Neurology, 67(8), 1476–1478.PubMedCrossRefGoogle Scholar
  87. Menasche, G., et al. (2000). Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nature Genetics, 25(2), 173–176.PubMedCrossRefGoogle Scholar
  88. Mesaki, K., et al. (2011). Fission of tubular endosomes triggers endosomal acidification and movement. PLoS ONE, 6(5), e19764.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Miaczynska, M., et al. (2004). APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell, 116(3), 445–456.PubMedCrossRefGoogle Scholar
  90. Mizoguchi, A., et al. (1990). Localization and subcellular distribution of smg p25A, a ras p21-like GTP-binding protein, in rat brain. Journal of Biological Chemistry, 265(20), 11872–11879.PubMedGoogle Scholar
  91. Mizuno-Yamasaki, E., Rivera-Molina, F., & Novick, P. (2012). GTPase networks in membrane traffic. Annual Review of Biochemistry, 81, 637–659.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Mori, Y., Fukuda, M., & Henley, J. M. (2014). Small GTPase Rab17 regulates the surface expression of kainate receptors but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal neurons via dendritic trafficking of Syntaxin-4 protein. Journal of Biological Chemistry, 289(30), 20773–20787.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Moritz, O. L., et al. (2001). Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death of transgenic Xenopus rods. Molecular Biology of the Cell, 12(8), 2341–2351.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Motoike, T., et al. (1990). Expression of smg p25A, a ras p21-like small GTP-binding protein, during postnatal development of rat cerebellum. Brain Research. Developmental Brain Research, 57(2), 279–289.PubMedCrossRefGoogle Scholar
  95. Munro, S. (2002). Organelle identity and the targeting of peripheral membrane proteins. Current Opinion in Cell Biology, 14(4), 506–514.PubMedCrossRefGoogle Scholar
  96. Nachury, M. V., et al. (2007). A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell, 129(6), 1201–1213.PubMedCrossRefGoogle Scholar
  97. Nakazawa, H., et al. (2012). Rab33a mediates anterograde vesicular transport for membrane exocytosis and axon outgrowth. Journal of Neuroscience, 32(37), 12712–12725.PubMedCrossRefGoogle Scholar
  98. Nixon, R. A. (2007). Autophagy, amyloidogenesis and Alzheimer disease. Journal of Cell Science, 120(Pt 23), 4081–4091.PubMedCrossRefGoogle Scholar
  99. Novick, P., & Zerial, M. (1997). The diversity of Rab proteins in vesicle transport. Current Opinion in Cell Biology, 9(4), 496–504.PubMedCrossRefGoogle Scholar
  100. Onnis, A., et al. (2015). The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis. Cell Death and Differentiation, 22(10), 1687–1699.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Opdam, F. J., et al. (2000). The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus. Journal of Cell Science, 113(Pt 15), 2725–2735.PubMedGoogle Scholar
  102. Ostermeier, C., & Brunger, A. T. (1999). Structural basis of Rab effector specificity: Crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A. Cell, 96(3), 363–374.PubMedCrossRefGoogle Scholar
  103. Park, M., et al. (2004). Recycling endosomes supply AMPA receptors for LTP. Science, 305(5692), 1972–1975.PubMedCrossRefGoogle Scholar
  104. Pereira-Leal, J. B., & Seabra, M. C. (2001). Evolution of the Rab family of small GTP-binding proteins. Journal of Molecular Biology, 313(4), 889–901.PubMedCrossRefGoogle Scholar
  105. Perez, R. G., Squazzo, S. L., & Koo, E. H. (1996). Enhanced release of amyloid beta-protein from codon 670/671 “Swedish” mutant beta-amyloid precursor protein occurs in both secretory and endocytic pathways. Journal of Biological Chemistry, 271(15), 9100–9107.PubMedCrossRefGoogle Scholar
  106. Pfeffer, S. R. (2001). Rab GTPases: Specifying and deciphering organelle identity and function. Trends in Cell Biology, 11(12), 487–491.PubMedCrossRefGoogle Scholar
  107. Pfeffer, S. R. (2013). Rab GTPase regulation of membrane identity. Current Opinion in Cell Biology, 25(4), 414–419.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Plutner, H., et al. (1991). Rab1b regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. Journal of Cell Biology, 115(1), 31–43.PubMedCrossRefGoogle Scholar
  109. Poirier, M. A., et al. (1998). The synaptic SNARE complex is a parallel four-stranded helical bundle. Natural Structural Biology, 5(9), 765–769.CrossRefGoogle Scholar
  110. Ponomareva, O. Y., Eliceiri, K. W., & Halloran, M. C. (2016). Charcot-Marie-Tooth 2b associated Rab7 mutations cause axon growth and guidance defects during vertebrate sensory neuron development. Neural Development, 11, 2.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Pylypenko, O., et al. (2006). Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling. EMBO Journal, 25(1), 13–23.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Ravikumar, B., et al. (2008). Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. Journal of Cell Science, 121(Pt 10), 1649–1660.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Reish, N. J., et al. (2014). Nucleotide bound to rab11a controls localization in rod cells but not interaction with rhodopsin. Journal of Neuroscience, 34(45), 14854–14863.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Ridge, P.G., M.T. Ebbert, and J.S. Kauwe, Genetics of Alzheimer’s disease. Biomed Res Int. 2013: p. 254954.Google Scholar
  115. Rink, J., et al. (2005). Rab conversion as a mechanism of progression from early to late endosomes. Cell, 122(5), 735–749.PubMedCrossRefGoogle Scholar
  116. Roosing, S., et al. (2013). Mutations in RAB28, encoding a farnesylated small GTPase, are associated with autosomal-recessive cone-rod dystrophy. American Journal of Human Genetics, 93(1), 110–117.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Roy, A., Kucukural, A., & Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols, 5(4), 725–738.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Sahlender, D. A., et al. (2005). Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. Journal of Cell Biology, 169(2), 285–295.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Sakane, A., Honda, K., & Sasaki, T. (2010). Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2. Molecular and Cellular Biology, 30(4), 1077–1087.PubMedCrossRefGoogle Scholar
  120. Sato, T., et al. (2014). Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis. J Cell Science, 127(Pt 2), 422–431.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Scheper, W., Zwart, R., & Baas, F. (2004). Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events. Brain Research. Molecular Brain Research, 122(1), 17–23.PubMedCrossRefGoogle Scholar
  122. Selkoe, D. J. (2004). Cell biology of protein misfolding: The examples of Alzheimer’s and Parkinson’s diseases. Nature Cell Biology, 6(11), 1054–1061.PubMedCrossRefGoogle Scholar
  123. Shetty, K. M., Kurada, P., & O’Tousa, J. E. (1998). Rab6 regulation of rhodopsin transport in Drosophila. Journal of Biological Chemistry, 273(32), 20425–20430.PubMedCrossRefGoogle Scholar
  124. Shirane, M., & Nakayama, K. I. (2006). Protrudin induces neurite formation by directional membrane trafficking. Science, 314(5800), 818–821.PubMedCrossRefGoogle Scholar
  125. Siniossoglou, S., & Pelham, H. R. (2001). An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes. EMBO Journal, 20(21), 5991–5998.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Spillantini, M. G., & Goedert, M. (2000). The alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Annals of the New York Academy of Sciences, 920, 16–27.PubMedCrossRefGoogle Scholar
  127. Spillantini, M. G., et al. (1997). Alpha-synuclein in Lewy bodies. Nature, 388(6645), 839–840.PubMedCrossRefGoogle Scholar
  128. Spillantini, M. G., et al. (1998). alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc Natl Acad Sci U S A, 95(11), 6469–6473.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Stafstrom, C. E., & Carmant, L. (2015). Seizures and epilepsy: An overview for neuroscientists. Cold Spring Harb Perspect Med., 5(6), a002426.CrossRefGoogle Scholar
  130. Star, E. N., Newton, A. J., & Murthy, V. N. (2005). Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function. Journal of Physiology, 569(Pt 1), 103–117.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Stenmark, H. (2009). Rab GTPases as coordinators of vesicle traffic. Nature Reviews Molecular Cell Biology, 10(8), 513–525.PubMedCrossRefGoogle Scholar
  132. Stenmark, H., et al. (1994). Distinct structural elements of rab5 define its functional specificity. EMBO Journal, 13(3), 575–583.PubMedPubMedCentralGoogle Scholar
  133. Sumakovic, M., et al. (2009). UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans. Journal of Cell Biology, 186(6), 897–914.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Sutton, R. B., et al. (1998). Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature, 395(6700), 347–353.PubMedCrossRefGoogle Scholar
  135. Syed, N., et al. (2001). Evaluation of retinal photoreceptors and pigment epithelium in a female carrier of choroideremia. Ophthalmology, 108(4), 711–720.PubMedCrossRefGoogle Scholar
  136. Szatmari, Z., & Sass, M. (2014). The autophagic roles of Rab small GTPases and their upstream regulators: A review. Autophagy, 10(7), 1154–1166.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Szodorai, A., et al. (2009). APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle. Journal of Neuroscience, 29(46), 14534–14544.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Takahashi, S., et al. (2011). Rab11 regulates exocytosis of recycling vesicles at the plasma membrane. J Cell Science, 125(Pt 17), 4049–4057.Google Scholar
  139. Takamori, S., et al. (2006). Molecular anatomy of a trafficking organelle. Cell, 127(4), 831–846.PubMedCrossRefGoogle Scholar
  140. Takano, T., et al. (2012). LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner. Journal of Neuroscience, 32(19), 6587–6599.PubMedCrossRefGoogle Scholar
  141. Tam, J. H., Seah, C., & Pasternak, S. H. (2014). The amyloid precursor protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid. Molecular Brain, 7, 54.PubMedPubMedCentralCrossRefGoogle Scholar
  142. Tan, M. G., et al. (2014). Decreased rabphilin 3A immunoreactivity in Alzheimer’s disease is associated with Abeta burden. Neurochemistry International, 64, 29–36.PubMedCrossRefGoogle Scholar
  143. Temtamy, S. A. (1966). Carpenter’s syndrome: Acrocephalopolysyndactyly. An autosomal recessive syndrome. J Pediatr, 69(1), 111–120.PubMedGoogle Scholar
  144. Tisdale, E. J., et al. (1992). GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. Journal of Cell Biology, 119(4), 749–761.PubMedCrossRefGoogle Scholar
  145. Tobin, J. L., & Beales, P. L. (2009). The nonmotile ciliopathies. Genetics in Medicine, 11(6), 386–402.PubMedCrossRefGoogle Scholar
  146. Tolmachova, T., et al. (2006). Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia. The Journal of Clinical Investigation, 116(2), 386–394.PubMedPubMedCentralCrossRefGoogle Scholar
  147. Touchot, N., Chardin, P., & Tavitian, A. (1987). Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: Molecular cloning of YPT-related cDNAs from a rat brain library. Proceedings of the National Academy of Sciences, 84(23), 8210–8214.CrossRefGoogle Scholar
  148. Udayar, V., et al. (2013). A paired RNAi and RabGAP overexpression screen identifies Rab11 as a regulator of beta-amyloid production. Cell Reports, 5(6), 1536–1551.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Ullrich, O., et al. (1996). Rab11 regulates recycling through the pericentriolar recycling endosome. Journal of Cell Biology, 135(4), 913–924.PubMedCrossRefGoogle Scholar
  150. Urbe, S., et al. (1993). Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells. FEBS Letters, 334(2), 175–182.PubMedCrossRefGoogle Scholar
  151. van den Hurk, J. A., et al. (1997). Molecular basis of choroideremia (CHM): Mutations involving the Rab escort protein-1 (REP-1) gene. Human Mutation, 9(2), 110–117.PubMedCrossRefGoogle Scholar
  152. Vetter, I. R., & Wittinghofer, A. (2001). The guanine nucleotide-binding switch in three dimensions. Science, 294(5545), 1299–1304.PubMedCrossRefGoogle Scholar
  153. Villarroel-Campos, D., et al. (2016). Rab35 functions in axon elongation are regulated by P53-related protein kinase in a mechanism that involves Rab35 protein degradation and the microtubule-associated protein 1B. Journal of Neuroscience, 36(27), 7298–7313.PubMedCrossRefGoogle Scholar
  154. Vonderheit, A., & Helenius, A. (2005). Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biology, 3(7), e233.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Walker, F. O. (2007). Huntington’s disease. Lancet, 369(9557), 218–228.PubMedCrossRefGoogle Scholar
  156. Wang, T., et al. (2011). Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization. Developmental Cell, 21(3), 431–444.PubMedCrossRefGoogle Scholar
  157. Wang, J., et al. (2015). Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling. Proceedings of the National Academy of Sciences, 112(1), 148–153.CrossRefGoogle Scholar
  158. Wanschers, B. F., et al. (2007). A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Experimental Cell Research, 313(16), 3408–3420.PubMedCrossRefGoogle Scholar
  159. Wilson, S. M., et al. (2000). A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proceedings of the National Academy of Sciences, 97(14), 7933–7938.CrossRefGoogle Scholar
  160. Wilson, G. R., et al. (2014). Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with alpha-synuclein pathology. The American Journal of Human Genetics, 95(6), 729–735.CrossRefGoogle Scholar
  161. Wu, F., & Yao, P. J. (2009). Clathrin-mediated endocytosis and Alzheimer’s disease: An update. Ageing Res Rev, 8(3), 147–149.PubMedCrossRefGoogle Scholar
  162. Wu, X., et al. (2002). Rab27a is an essential component of melanosome receptor for myosin Va. Molecular Biology of the Cell, 13(5), 1735–1749.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Wucherpfennig, T., Wilsch-Brauninger, M., & Gonzalez-Gaitan, M. (2003). Role of Drosophila Rab5 during endosomal trafficking at the synapse and evoked neurotransmitter release. Journal of Cell Biology, 161(3), 609–624.PubMedPubMedCentralCrossRefGoogle Scholar
  164. Yang, J., et al. (2015). The I-TASSER suite: Protein structure and function prediction. Nature Methods, 12(1), 7–8.PubMedPubMedCentralCrossRefGoogle Scholar
  165. Yoshimura, S., et al. (2007). Functional dissection of Rab GTPases involved in primary cilium formation. Journal of Cell Biology, 178(3), 363–369.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Zerial, M., & McBride, H. (2001). Rab proteins as membrane organizers. Nature Reviews Molecular Cell Biology, 2(2), 107–117.PubMedCrossRefGoogle Scholar
  167. Zhang, Y. (2008). I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, 9, 40.PubMedPubMedCentralCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Biochemistry and Molecular Mechanisms Lab, APTD, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Council of Scientific and Industrial Research (CSIR)Ministry of Science and Technology, Government of IndiaThiruvananthapuramIndia
  2. 2.Molecular Medicine, Applied Biology, Biomedical Technology WingSree Chitra Tirunal Institute for Medical Sciences and TechnologyThiruvananthapuramIndia
  3. 3.Field Neurosciences Institute Laboratory for Restorative Neurology, Program in Neuroscience, Department of PsychologyCentral Michigan UniversityMt. PleasantUSA

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