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


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.


Membrane anchoring Rab proteins Molecular switches Synaptic vesicles Exocytosis Neurodegeneration 





Alzheimer’s disease

Amyloid beta protein


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


Amyloid precursor proteins


Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper


Bardet–Biedl syndrome


Brain-derived neurotropic factor


Triplet nucleotide codes for glutamine


Clathrin-coated vesicles


Charcot–Marie–Tooth-type 2B


Cone-rod dystrophy


Carpenter syndrome




Differentially expressed in normal and neoplastic cells


Early endosomes


Early endosome adapter1


Glutamate/cysteine transporter


Endoplasmic reticulum


GTP hydrolysis activator protein


Golgi complex


Guanosine diphosphate


Guanine nucleotide exchange factor


Glucose transporter


Guanosine triphosphate


Griscelli syndrome




Huntington’s disease




Huntingtin protein


Intraflagellar transport


Lewy body disease


Late endosome


Leucine-rich repeat kinase 2


Long-term potentiation


Long-term depression


Mitochondria-associated membranes


Mutant Huntingtin protein


Martsolf syndrome


Medium spiny neurons


N-acetyl d-aspartate


N-acetyl d-aspartate receptor


N-ethylmaleimide-sensitive factor


Parkinson’s disease






Rab-interacting protein GDP-dissociation inhibitor


Rab escort protein


Retinal pigment epithelium


Ras genes from rat brain


Rab3A effector Rabphilin-3A


Recycling endosome


Substantia nigra pars compacta


Synaptic vesicle


Trans-Golgi network


Transmembrane protein 230


Tyrosine kinase-B


Target-soluble NSF attachment protein receptor


Vesicle associated membrane protein


Vesicle-soluble NSF attachment protein receptor




Yeast-related protein



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.


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.


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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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