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The Role of Integrins at Synapses

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The Sticky Synapse

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Abstract

Integrins are transmembrane, adhesive receptors that serve as functional links between the extracellular matrix and the intracellular environment. Integrin engagement of a ligand can activate intracellular signaling pathways that regulate many cellular processes. The adhesive and signaling properties of integrins make them ideal for modulating connections at specialized adhesive junctions, such as synapses. Indeed, integrins are emerging as critical regulators of synaptic connections in the brain and the peripheral nervous system.

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References

  • Allen KM, Gleeson JG, Bagrodia S et al. (1998) PAK3 mutation in nonsyndromic X-linked mental retardation. Nat Genet 20:25–30

    Article  CAS  PubMed  Google Scholar 

  • Anderson KL and Ferreira A (2004) alpha1 Integrin activation: a link between beta-amyloid deposition and neuronal death in aging hippocampal neurons. J Neurosci Res 75:688–697

    Article  CAS  PubMed  Google Scholar 

  • Anderson MJ, Shi ZQ and Zackson SL (1996) Proteolytic disruption of laminin-integrin complexes on muscle cells during synapse formation. Mol Cell Biol 16:4972–4984

    CAS  PubMed  Google Scholar 

  • Bahr BA and Lynch G (1992) Purification of an Arg-Gly-Asp selective matrix receptor from brain synaptic plasma membranes. Biochem J 281 (Pt 1):137–142

    CAS  PubMed  Google Scholar 

  • Bahr BA, Sheppard A and Lynch G (1991) Fibronectin binding by brain synaptosomal membranes may not involve conventional integrins. Neuroreport 2:13–16

    Article  CAS  PubMed  Google Scholar 

  • Bernard-Trifilo JA, Kramar EA, Torp R et al. (2005) Integrin signaling cascades are operational in adult hippocampal synapses and modulate NMDA receptor physiology. J Neurochem 93:834–849

    Article  CAS  PubMed  Google Scholar 

  • Beumer K, Matthies HJ, Bradshaw A et al. (2002) Integrins regulate DLG/FAS2 via a CaM kinase II-dependent pathway to mediate synapse elaboration and stabilization during postembryonic development. Development 129:3381–3391

    CAS  PubMed  Google Scholar 

  • Beumer KJ, Rohrbough J, Prokop A et al. (1999) A role for PS integrins in morphological growth and synaptic function at the postembryonic neuromuscular junction of Drosophila. Development 126:5833–5846

    CAS  PubMed  Google Scholar 

  • Bi X, Gall CM, Zhou J et al. (2002) Uptake and pathogenic effects of amyloid beta peptide 1–42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists. Neuroscience 112:827–840

    Article  CAS  PubMed  Google Scholar 

  • Bliss TV and Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356

    CAS  PubMed  Google Scholar 

  • Bourgin C, Murai KK, Richter M et al. (2007) The EphA4 receptor regulates dendritic spine remodeling by affecting beta1-integrin signaling pathways. J Cell Biol 178:1295–1307

    Article  CAS  PubMed  Google Scholar 

  • Bredt DS and Nicoll RA (2003) AMPA receptor trafficking at excitatory synapses. Neuron 40:361–379

    Article  CAS  PubMed  Google Scholar 

  • Burkin DJ, Gu M, Hodges BL et al. (1998) A functional role for specific spliced variants of the alpha7beta1 integrin in acetylcholine receptor clustering. J Cell Biol 143:1067–1075

    Article  CAS  PubMed  Google Scholar 

  • Burkin DJ, Kim JE, Gu M et al. (2000) Laminin and alpha7beta1 integrin regulate agrin-induced clustering of acetylcholine receptors. J Cell Sci 113 (Pt 16):2877–2886

    CAS  PubMed  Google Scholar 

  • Chan CS, Levenson JM, Mukhopadhyay PS et al. (2007) Alpha3-integrins are required for hippocampal long-term potentiation and working memory. Learn Mem 14:606–615

    Article  CAS  PubMed  Google Scholar 

  • Chan CS, Weeber EJ, Kurup S et al. (2003) Integrin requirement for hippocampal synaptic plasticity and spatial memory. J Neurosci 23:7107–7116

    CAS  PubMed  Google Scholar 

  • Chan CS, Weeber EJ, Zong L et al. (2006) Beta 1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory. J Neurosci 26:223–232

    Article  CAS  PubMed  Google Scholar 

  • Chavis P and Westbrook G (2001) Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse. Nature 411:317–321

    Article  CAS  PubMed  Google Scholar 

  • Chen BM and Grinnell AD (1995) Integrins and modulation of transmitter release from motor nerve terminals by stretch. Science 269:1578–1580

    Article  CAS  PubMed  Google Scholar 

  • Chun D, Gall CM, Bi X et al. (2001) Evidence that integrins contribute to multiple stages in the consolidation of long term potentiation in rat hippocampus. Neuroscience 105:815–829

    Article  CAS  PubMed  Google Scholar 

  • Cingolani LA, Thalhammer A, Yu LM et al. (2008) Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta3 integrins. Neuron 58:749–762

    Article  CAS  PubMed  Google Scholar 

  • Cohen MW, Hoffstrom BG and DeSimone DW (2000) Active zones on motor nerve terminals contain alpha 3beta 1 integrin. J Neurosci 20:4912–4921

    CAS  PubMed  Google Scholar 

  • Coleman P, Federoff H and Kurlan R (2004) A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63:1155–1162

    PubMed  Google Scholar 

  • Einheber S, Schnapp LM, Salzer JL et al. (1996) Regional and ultrastructural distribution of the alpha 8 integrin subunit in developing and adult rat brain suggests a role in synaptic function. J Comp Neurol 370:105–134

    Article  CAS  PubMed  Google Scholar 

  • Fiala JC, Spacek J and Harris KM (2002) Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res. Brain Res. Rev. 39:29–54

    Article  PubMed  Google Scholar 

  • Fox MA (this volume) Development of the vertebrate neuromuscular junction. In Hortsch M and Umemori H (eds) The sticky synapse, Springer, New York

    Google Scholar 

  • Gautam M, Noakes PG, Moscoso L et al. (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85:525–535

    Article  CAS  PubMed  Google Scholar 

  • Grosshans DR and Browning MD (2001) Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor. J Neurochem 76:737–744

    Article  CAS  PubMed  Google Scholar 

  • Grotewiel MS, Beck CD, Wu KH et al. (1998) Integrin-mediated short-term memory in Drosophila. Nature 391:455–460

    Article  CAS  PubMed  Google Scholar 

  • Hisatsune C, Umemori H, Mishina M et al. (1999) Phosphorylation-dependent interaction of the N-methyl-D-aspartate receptor epsilon 2 subunit with phosphatidylinositol 3-kinase. Genes Cells 4:657–666

    Article  CAS  PubMed  Google Scholar 

  • Huang EP (1998) Synaptic plasticity: going through phases with LTP. Curr Biol 8:R350–352

    Article  CAS  PubMed  Google Scholar 

  • Huang Z, Shimazu K, Woo NH et al. (2006) Distinct roles of the beta 1-class integrins at the developing and the mature hippocampal excitatory synapse. J Neurosci 26:11208–11219

    Article  CAS  PubMed  Google Scholar 

  • Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687

    Article  CAS  PubMed  Google Scholar 

  • Kashani AH, Chen BM and Grinnell AD (2001) Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins. J Physiol 530:243–252

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi SY and Hirano T (2006) Integrin alpha3beta1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron. Mol Cell Neurosci 31:416–426

    Article  CAS  PubMed  Google Scholar 

  • Kramar EA, Bernard JA, Gall CM et al. (2002) Alpha3 integrin receptors contribute to the consolidation of long-term potentiation. Neuroscience 110:29–39

    Article  CAS  PubMed  Google Scholar 

  • Kutsche K, Yntema H, Brandt A et al. (2000) Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. Nat Genet 26:247–250

    Article  CAS  PubMed  Google Scholar 

  • Lin B, Arai AC, Lynch G et al. (2003) Integrins regulate NMDA receptor-mediated synaptic currents. J Neurophysiol 89:2874–2878

    Article  CAS  PubMed  Google Scholar 

  • Lin CY, Hilgenberg LG, Smith MA et al. (2008) Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores. Mol Cell Neurosci 37:770–780

    Article  CAS  PubMed  Google Scholar 

  • Lin CY, Lynch G and Gall CM (2005) AMPA receptor stimulation increases alpha5beta1 integrin surface expression, adhesive function and signaling. J Neurochem 94:531–546

    Article  CAS  PubMed  Google Scholar 

  • Lin W, Burgess RW, Dominguez B et al. (2001) Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature 410:1057–1064

    Article  CAS  PubMed  Google Scholar 

  • Luo BH, Carman CV and Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647

    Article  CAS  PubMed  Google Scholar 

  • Martin PT, Kaufman SJ, Kramer RH et al. (1996) Synaptic integrins in developing, adult, and mutant muscle: selective association of alpha1, alpha7A, and alpha7B integrins with the neuromuscular junction. Dev Biol 174:125–139

    Article  CAS  PubMed  Google Scholar 

  • Martin PT and Sanes JR (1997) Integrins mediate adhesion to agrin and modulate agrin signaling. Development 124:3909–3917

    CAS  PubMed  Google Scholar 

  • Matus A, Ackermann M, Pehling G et al. (1982) High actin concentrations in brain dendritic spines and postsynaptic densities. Proc Natl Acad Sci USA 79:7590–7594

    Article  CAS  PubMed  Google Scholar 

  • Miranti CK and Brugge JS (2002) Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol 4:E83–E90

    Article  CAS  PubMed  Google Scholar 

  • Nishimura SL, Boylen KP, Einheber S et al. (1998) Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat brain. Brain Res 791:271–282

    Article  CAS  PubMed  Google Scholar 

  • Ramakers GJ (2002) Rho proteins, mental retardation and the cellular basis of cognition. Trends Neurosci 25:191–199

    Article  CAS  PubMed  Google Scholar 

  • Rohrbough J, Grotewiel MS, Davis RL et al. (2000) Integrin-mediated regulation of synaptic morphology, transmission, and plasticity. J Neurosci 20:6868–6878

    CAS  PubMed  Google Scholar 

  • Schwander M, Shirasaki R, Pfaff SL et al. (2004) Beta1 integrins in muscle, but not in motor neurons, are required for skeletal muscle innervation. J Neurosci 24:8181–8191

    Article  CAS  PubMed  Google Scholar 

  • Schwartz MA and Shattil SJ (2000) Signaling networks linking integrins and rho family GTPases. Trends Biochem Sci 25:388–391

    Article  CAS  PubMed  Google Scholar 

  • Shepherd JD and Huganir RL (2007) The cell biology of synaptic plasticity: AMPA receptor trafficking. Annu Rev Cell Dev Biol 23:613–643

    Article  CAS  PubMed  Google Scholar 

  • Shi Y and Ethell IM (2006) Integrins control dendritic spine plasticity in hippocampal neurons through NMDA receptor and Ca2+/calmodulin-dependent protein kinase II-mediated actin reorganization. J Neurosci 26:1813–1822

    Article  CAS  PubMed  Google Scholar 

  • Staubli U, Chun D and Lynch G (1998) Time-dependent reversal of long-term potentiation by an integrin antagonist. J Neurosci 18:3460–3469

    CAS  PubMed  Google Scholar 

  • Staubli U, Vanderklish P and Lynch G (1990) An inhibitor of integrin receptors blocks long-term potentiation. Behav Neural Biol 53:1–5

    Article  CAS  PubMed  Google Scholar 

  • Stephan A, Laroche S and Davis S (2001) Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits. J Neurosci 21:5703–5714

    CAS  PubMed  Google Scholar 

  • Suzuki K, Grinnell AD and Kidokoro Y (2002) Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A. J Physiol 538:103–119

    Article  CAS  PubMed  Google Scholar 

  • Watson PM, Humphries MJ, Relton J et al. (2007) Integrin-binding RGD peptides induce rapid intracellular calcium increases and MAPK signaling in cortical neurons. Mol Cell Neurosci 34:147–154

    Article  CAS  PubMed  Google Scholar 

  • Webb DJ, Zhang H, Majumdar D et al. (2007) alpha5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons. J Biol Chem 282:6929–6935

    Article  CAS  PubMed  Google Scholar 

  • Xiao P, Bahr BA, Staubli U et al. (1991) Evidence that matrix recognition contributes to stabilization but not induction of LTP. Neuroreport 2:461–464

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grant MH071674 from NIH to D.J.W.

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  1. Department of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, VU station B, 37235, Box 35-1634, Nashville, TN, USA

    Devi Majumdar & Donna J. Webb

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  1. Devi Majumdar
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Correspondence to Donna J. Webb .

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    Majumdar, D., Webb, D.J. (2009). The Role of Integrins at Synapses. In: Umemori, H., Hortsch, M. (eds) The Sticky Synapse. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92708-4_19

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