Skip to main content
SpringerLink
Log in

Principles Driving the Spatial Organization of Rho GTPase Signaling at Synapses

  • Chapter
  • First Online:
Ras Superfamily Small G Proteins: Biology and Mechanisms 1

  • 1389 Accesses

Abstract

The Rho proteins play critical roles in numerous aspects of neuronal development, and mutations in their regulators (GEFs and GAPs) and effectors underlie multiple neurodevelopmental and neurological disorders. How Rho GTPase-mediated signaling can have a hand in regulating so many different neurobiological processes remains a challenging question. An emerging theme is that GAPs and GEFs, through their spatial/temporal regulation and/or through additional protein–protein interactions, cooperate in making connections between upstream signals and the downstream signaling output, engaging distinct effector proteins. This chapter focuses on recent evidence illustrating distinct modes of regulation and specialized roles of Rho regulators particularly in the context of synaptic structure, function, and plasticity, and how their dysregulation affects behavioral processes and contributes to disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdul-Manan N, Aghazadeh B, Liu GA, Majumdar A, Ouerfelli O, Siminovitch KA, Rosen MK (1999) Structure of Cdc42 in complex with the GTPase-binding domain of the ‘Wiskott-Aldrich syndrome’ protein. Nature 399(6734):379–383. doi:10.1038/20726

    CAS  PubMed  Google Scholar 

  • Addington AM, Rapoport JL (2009) The genetics of childhood-onset schizophrenia: when madness strikes the prepubescent. Curr Psychiatry Rep 11(2):156–161

    PubMed Central  PubMed  Google Scholar 

  • Ahmad KF, Lim WA (2010) The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin. PLoS One 5(6):e11291. doi:10.1371/journal.pone.0011291

    PubMed Central  PubMed  Google Scholar 

  • Ahmed S (2011) Nanoscopy of cell architecture: the actin-membrane interface. Bioarchitecture 1(1):32–38. doi:10.4161/bioa.1.1.14799

    PubMed Central  PubMed  Google Scholar 

  • Bayer KU, De Koninck P, Leonard AS, Hell JW, Schulman H (2001) Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 411(6839):801–805. doi:10.1038/35081080

    CAS  PubMed  Google Scholar 

  • Benesch S, Polo S, Lai FP, Anderson KI, Stradal TE, Wehland J, Rottner K (2005) N-WASP deficiency impairs EGF internalization and actin assembly at clathrin-coated pits. J Cell Sci 118(Pt 14):3103–3115. doi:10.1242/jcs.02444

    CAS  PubMed  Google Scholar 

  • Bergmann C, Zerres K, Senderek J, Rudnik-Schoneborn S, Eggermann T, Hausler M, Mull M, Ramaekers VT (2003) Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. Brain 126(Pt 7):1537–1544. doi:10.1093/brain/awg173

    PubMed  Google Scholar 

  • Billuart P, Bienvenu T, Ronce N, des Portes V, Vinet MC, Zemni R, Roest Crollius H, Carrie A, Fauchereau F, Cherry M, Briault S, Hamel B, Fryns JP, Beldjord C, Kahn A, Moraine C, Chelly J (1998) Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392(6679):923–926. doi:10.1038/31940

    CAS  PubMed  Google Scholar 

  • Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348(Pt 2):241–255

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boda B, Dubos A, Muller D (2010) Signaling mechanisms regulating synapse formation and function in mental retardation. Curr Opin Neurobiol 20(4):519–527. doi:10.1016/j.conb.2010.03.012

    CAS  PubMed  Google Scholar 

  • Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: critical elements in the control of small G proteins. Cell 129(5):865–877. doi:10.1016/j.cell.2007.05.018

    CAS  PubMed  Google Scholar 

  • Boulter E, Garcia-Mata R, Guilluy C, Dubash A, Rossi G, Brennwald PJ, Burridge K (2010) Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1. Nat Cell Biol 12(5):477–483. doi:10.1038/ncb2049

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bradley WD, Hernandez SE, Settleman J, Koleske AJ (2006) Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane. Mol Biol Cell 17(11):4827–4836. doi:10.1091/mbc.E06-02-0132

    CAS  PubMed Central  PubMed  Google Scholar 

  • Burbelo PD, Drechsel D, Hall A (1995) A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem 270(49):29071–29074

    CAS  PubMed  Google Scholar 

  • Carlisle HJ, Kennedy MB (2005) Spine architecture and synaptic plasticity. Trends Neurosci 28(4):182–187. doi:10.1016/j.tins.2005.01.008

    CAS  PubMed  Google Scholar 

  • Carlson BR, Lloyd KE, Kruszewski A, Kim IH, Rodriguiz RM, Heindel C, Faytell M, Dudek SM, Wetsel WC, Soderling SH (2011) WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory. J Neurosci 31(7):2447–2460. doi:10.1523/JNEUROSCI.4433-10.2011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Charrier C, Joshi K, Coutinho-Budd J, Kim JE, Lambert N, de Marchena J, Jin WL, Vanderhaeghen P, Ghosh A, Sassa T, Polleux F (2012) Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149(4):923–935. doi:10.1016/j.cell.2012.03.034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cherfils J, Zeghouf M (2013) Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev 93(1):269–309. doi:10.1152/physrev.00003.2012

    CAS  PubMed  Google Scholar 

  • Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62–74. doi:10.1038/nrm2816

    CAS  PubMed  Google Scholar 

  • Choi KY, Kim HK, Lee SY, Moon KH, Sim SS, Kim JW, Chung HK, Rhee SG (1990) Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase. Science 248(4951):64–66

    CAS  PubMed  Google Scholar 

  • Cingolani LA, Goda Y (2008) Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 9(5):344–356. doi:10.1038/nrn2373

    CAS  PubMed  Google Scholar 

  • Colgan LA, Yasuda R (2013) Plasticity of dendritic spines: subcompartmentalization of signaling. Annu Rev Physiol. doi:10.1146/annurev-physiol-021113-170400

    PubMed  Google Scholar 

  • Cook DR, Rossman KL, Der CJ (2013) Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease. Oncogene. doi:10.1038/onc.2013.362

    PubMed Central  Google Scholar 

  • Coyle JT, Tsai G, Goff D (2003) Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann N Y Acad Sci 1003:318–327

    CAS  PubMed  Google Scholar 

  • Dalva MB, Takasu MA, Lin MZ, Shamah SM, Hu L, Gale NW, Greenberg ME (2000) EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103(6):945–956

    CAS  PubMed  Google Scholar 

  • DeGeer J, Lamarche-Vane N (2013) Rho GTPases in neurodegeneration diseases. Exp Cell Res 319(15):2384–2394. doi:10.1016/j.yexcr.2013.06.016

    CAS  PubMed  Google Scholar 

  • Dennis MY, Nuttle X, Sudmant PH, Antonacci F, Graves TA, Nefedov M, Rosenfeld JA, Sajjadian S, Malig M, Kotkiewicz H, Curry CJ, Shafer S, Shaffer LG, de Jong PJ, Wilson RK, Eichler EE (2012) Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149(4):912–922. doi:10.1016/j.cell.2012.03.033

    CAS  PubMed Central  PubMed  Google Scholar 

  • des Portes V, Boddaert N, Sacco S, Briault S, Maincent K, Bahi N, Gomot M, Ronce N, Bursztyn J, Adamsbaum C, Zilbovicius M, Chelly J, Moraine C (2004) Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene. Am J Med Genet A 124A(4):364–371. doi:10.1002/ajmg.a.20422

    PubMed  Google Scholar 

  • Dietz DM, Sun H, Lobo MK, Cahill ME, Chadwick B, Gao V, Koo JW, Mazei-Robison MS, Dias C, Maze I, Damez-Werno D, Dietz KC, Scobie KN, Ferguson D, Christoffel D, Ohnishi Y, Hodes GE, Zheng Y, Neve RL, Hahn KM, Russo SJ, Nestler EJ (2012) Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons. Nat Neurosci. doi:10.1038/nn.3094

    Google Scholar 

  • Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899):790–793. doi:10.1038/nature00859

    CAS  PubMed  Google Scholar 

  • Endris V, Wogatzky B, Leimer U, Bartsch D, Zatyka M, Latif F, Maher ER, Tariverdian G, Kirsch S, Karch D, Rappold GA (2002) The novel Rho-GTPase activating gene MEGAP/srGAP3 has a putative role in severe mental retardation. Proc Natl Acad Sci USA 99(18):11754–11759. doi:10.1073/pnas.162241099

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fischer M, Kaech S, Wagner U, Brinkhaus H, Matus A (2000) Glutamate receptors regulate actin-based plasticity in dendritic spines. Nat Neurosci 3(9):887–894. doi:10.1038/78791

    CAS  PubMed  Google Scholar 

  • Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ (1998) Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif. J Biol Chem 273(5):2698–2705

    CAS  PubMed  Google Scholar 

  • Govek EE, Newey SE, Akerman CJ, Cross JR, Van der Veken L, Van Aelst L (2004) The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. Nat Neurosci 7(4):364–372. doi:10.1038/nn1210

    CAS  PubMed  Google Scholar 

  • Govek EE, Newey SE, Van Aelst L (2005) The role of the Rho GTPases in neuronal development. Genes Dev 19(1):1–49. doi:10.1101/gad.1256405

    CAS  PubMed  Google Scholar 

  • Guan KL, Rao Y (2003) Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci 4(12):941–956. doi:10.1038/nrn1254

    CAS  PubMed  Google Scholar 

  • Guerrier S, Coutinho-Budd J, Sassa T, Gresset A, Jordan NV, Chen K, Jin WL, Frost A, Polleux F (2009) The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis. Cell 138(5):990–1004. doi:10.1016/j.cell.2009.06.047

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hall A (2012) Rho family GTPases. Biochem Soc Trans 40(6):1378–1382. doi:10.1042/BST20120103

    CAS  PubMed  Google Scholar 

  • Hall A, Lalli G (2010) Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol 2(2):a001818. doi:10.1101/cshperspect.a001818

    PubMed Central  PubMed  Google Scholar 

  • Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Luscher B, Rees MI, Harvey RJ (2004) The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci 24(25):5816–5826. doi:10.1523/JNEUROSCI.1184-04.2004

    CAS  PubMed  Google Scholar 

  • Hayashi-Takagi A, Takaki M, Graziane N, Seshadri S, Murdoch H, Dunlop AJ, Makino Y, Seshadri AJ, Ishizuka K, Srivastava DP, Xie Z, Baraban JM, Houslay MD, Tomoda T, Brandon NJ, Kamiya A, Yan Z, Penzes P, Sawa A (2010) Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat Neurosci 13(3):327–332. doi:10.1038/nn.2487

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hernandez SE, Settleman J, Koleske AJ (2004) Adhesion-dependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase. Curr Biol 14(8):691–696. doi:10.1016/j.cub.2004.03.062

    CAS  PubMed  Google Scholar 

  • Hoefen RJ, Berk BC (2006) The multifunctional GIT family of proteins. J Cell Sci 119(Pt 8):1469–1475. doi:10.1242/jcs.02925

    CAS  PubMed  Google Scholar 

  • Hotulainen P, Llano O, Smirnov S, Tanhuanpaa K, Faix J, Rivera C, Lappalainen P (2009) Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol 185(2):323–339. doi:10.1083/jcb.200809046

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hruska M, Dalva MB (2012) Ephrin regulation of synapse formation, function and plasticity. Mol Cell Neurosci 50(1):35–44. doi:10.1016/j.mcn.2012.03.004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huganir RL, Nicoll RA (2013) AMPARs and Synaptic Plasticity: The Last 25 Years. Neuron 80(3):704–717. doi:10.1016/j.neuron.2013.10.025

    CAS  PubMed  Google Scholar 

  • Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS (2001) Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3(10):927–932. doi:10.1038/ncb1001-927

    CAS  PubMed  Google Scholar 

  • Impey S, Davare M, Lesiak A, Fortin D, Ando H, Varlamova O, Obrietan K, Soderling TR, Goodman RH, Wayman GA (2010) An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling. Mol Cell Neurosci 43(1):146–156. doi:10.1016/j.mcn.2009.10.005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Irie F, Yamaguchi Y (2002) EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Nat Neurosci 5(11):1117–1118. doi:10.1038/nn964

    CAS  PubMed  Google Scholar 

  • Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986) The inositol tris/tetrakisphosphate pathway–demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues. Nature 320(6063):631–634. doi:10.1038/320631a0

    CAS  PubMed  Google Scholar 

  • Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269. doi:10.1146/annurev.cellbio.21.020604.150721

    CAS  PubMed  Google Scholar 

  • Kalscheuer VM, Musante L, Fang C, Hoffmann K, Fuchs C, Carta E, Deas E, Venkateswarlu K, Menzel C, Ullmann R, Tommerup N, Dalpra L, Tzschach A, Selicorni A, Luscher B, Ropers HH, Harvey K, Harvey RJ (2009) A balanced chromosomal translocation disrupting ARHGEF9 is associated with epilepsy, anxiety, aggression, and mental retardation. Hum Mutat 30(1):61–68. doi:10.1002/humu.20814

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kang MG, Guo Y, Huganir RL (2009) AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade. Proc Natl Acad Sci U S A 106(9):3549–3554. doi:10.1073/pnas.0812861106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kemp A, Manahan-Vaughan D (2007) Hippocampal long-term depression: master or minion in declarative memory processes? Trends Neurosci 30(3):111–118. doi:10.1016/j.tins.2007.01.002

    CAS  PubMed  Google Scholar 

  • Kerrisk ME, Koleske AJ (2013) Arg kinase signaling in dendrite and synapse stabilization pathways: memory, cocaine sensitivity, and stress. Int J Biochem Cell Biol 45(11):2496–2500. doi:10.1016/j.biocel.2013.07.018

    CAS  PubMed  Google Scholar 

  • Kessels HW, Malinow R (2009) Synaptic AMPA receptor plasticity and behavior. Neuron 61(3):340–350. doi:10.1016/j.neuron.2009.01.015

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim E, Sheng M (2004) PDZ domain proteins of synapses. Nat Rev Neurosci 5(10):771–781. doi:10.1038/nrn1517

    CAS  PubMed  Google Scholar 

  • Kim IH, Park SK, Hong ST, Jo YS, Kim EJ, Park EH, Han SB, Shin HS, Sun W, Kim HT, Soderling SH, Kim H (2009) Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling. J Neurosci 29(44):14039–14049. doi:10.1523/JNEUROSCI.2483-09.2009

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kins S, Betz H, Kirsch J (2000) Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci 3(1):22–29. doi:10.1038/71096

    CAS  PubMed  Google Scholar 

  • Kiraly DD, Eipper-Mains JE, Mains RE, Eipper BA (2010a) Synaptic plasticity, a symphony in GEF. ACS Chem Neurosci 1(5):348–365. doi:10.1021/cn100012x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kiraly DD, Ma XM, Mazzone CM, Xin X, Mains RE, Eipper BA (2010b) Behavioral and morphological responses to cocaine require kalirin7. Biol Psychiatry 68(3):249–255. doi:10.1016/j.biopsych.2010.03.024

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kiraly DD, Lemtiri-Chlieh F, Levine ES, Mains RE, Eipper BA (2011) Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic localization and function. J Neurosci 31(35):12554–12565. doi:10.1523/JNEUROSCI.3143-11.2011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kishino T, Lalande M, Wagstaff J (1997) UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 15(1):70–73. doi:10.1038/ng0197-70

    CAS  PubMed  Google Scholar 

  • Lai KO, Ip NY (2009) Synapse development and plasticity: roles of ephrin/Eph receptor signaling. Curr Opin Neurobiol 19(3):275–283. doi:10.1016/j.conb.2009.04.009

    CAS  PubMed  Google Scholar 

  • Lai KO, Ip NY (2013) Structural plasticity of dendritic spines: the underlying mechanisms and its dysregulation in brain disorders. Biochim Biophys Acta 1832(12):2257–2263. doi:10.1016/j.bbadis.2013.08.012

    CAS  PubMed  Google Scholar 

  • Lamprecht R, Farb CR, LeDoux JE (2002) Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex. Neuron 36(4):727–738

    CAS  PubMed  Google Scholar 

  • Lemtiri-Chlieh F, Zhao L, Kiraly DD, Eipper BA, Mains RE, Levine ES (2011) Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity. BMC Neurosci 12:126. doi:10.1186/1471-2202-12-126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lesca G, Till M, Labalme A, Vallee D, Hugonenq C, Philip N, Edery P, Sanlaville D (2011) De novo Xq11.11 microdeletion including ARHGEF9 in a boy with mental retardation, epilepsy, macrosomia, and dysmorphic features. Am J Med Genet A 155A(7):1706–1711. doi:10.1002/ajmg.a.34004

    PubMed  Google Scholar 

  • Lin YC, Yeckel MF, Koleske AJ (2013) Abl2/Arg controls dendritic spine and dendrite arbor stability via distinct cytoskeletal control pathways. J Neurosci 33(5):1846–1857. doi:10.1523/JNEUROSCI.4284-12.2013

    CAS  PubMed Central  PubMed  Google Scholar 

  • Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1(3):173–180. doi:10.1038/35044547

    CAS  PubMed  Google Scholar 

  • Luscher C, Huber KM (2010) Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 65(4):445–459. doi:10.1016/j.neuron.2010.01.016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Madaule P, Axel R (1985) A novel ras-related gene family. Cell 41(1):31–40

    CAS  PubMed  Google Scholar 

  • Marco EJ, Abidi FE, Bristow J, Dean WB, Cotter P, Jeremy RJ, Schwartz CE, Sherr EH (2008) ARHGEF9 disruption in a female patient is associated with X linked mental retardation and sensory hyperarousal. J Med Genet 45(2):100–105. doi:10.1136/jmg.2007.052324

    CAS  PubMed  Google Scholar 

  • Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, Greer PL, Bikoff JB, Ho HY, Soskis MJ, Sahin M, Greenberg ME (2010) EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell 143(3):442–455. doi:10.1016/j.cell.2010.09.038

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mason FM, Heimsath EG, Higgs HN, Soderling SH (2011) Bi-modal regulation of a formin by srGAP2. J Biol Chem 286(8):6577–6586. doi:10.1074/jbc.M110.190397

    CAS  PubMed Central  PubMed  Google Scholar 

  • Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, Rommens JM, Beaudet AL (1997) De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet 15(1):74–77. doi:10.1038/ng0197-74

    CAS  PubMed  Google Scholar 

  • McKinney RA, Capogna M, Durr R, Gahwiler BH, Thompson SM (1999) Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nat Neurosci 2(1):44–49. doi:10.1038/4548

    CAS  PubMed  Google Scholar 

  • Menon P, Deane R, Sagare A, Lane SM, Zarcone TJ, O'Dell MR, Yan C, Zlokovic BV, Berk BC (2010) Impaired spine formation and learning in GPCR kinase 2 interacting protein-1 (GIT1) knockout mice. Brain Res 1317:218–226. doi:10.1016/j.brainres.2009.11.084

    CAS  PubMed Central  PubMed  Google Scholar 

  • Merrifield CJ, Qualmann B, Kessels MM, Almers W (2004) Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts. Eur J Cell Biol 83(1):13–18

    CAS  PubMed  Google Scholar 

  • Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 9(9):1415–1423

    CAS  PubMed  Google Scholar 

  • Mott HR, Nietlispach D, Evetts KA, Owen D (2005) Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK). Biochemistry 44(33):10977–10983. doi:10.1021/bi050374a

    CAS  PubMed  Google Scholar 

  • Murakoshi H, Wang H, Yasuda R (2011) Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature 472(7341):100–104. doi:10.1038/nature09823

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nadif Kasri N, Van Aelst L (2008) Rho-linked genes and neurological disorders. Pflugers Archiv 455(5):787–797. doi:10.1007/s00424-007-0385-1

    CAS  PubMed  Google Scholar 

  • Nadif Kasri N, Nakano-Kobayashi A, Malinow R, Li B, Van Aelst L (2009) The Rho-linked mental retardation protein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors. Genes Dev 23(11):1289–1302. doi:10.1101/gad.1783809

    PubMed Central  PubMed  Google Scholar 

  • Nadif Kasri N, Nakano-Kobayashi A, Van Aelst L (2011) Rapid synthesis of the X-linked mental retardation protein OPHN1 mediates mGluR-dependent LTD through interaction with the endocytic machinery. Neuron 72(2):300–315. doi:10.1016/j.neuron.2011.09.001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakayama AY, Harms MB, Luo L (2000) Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20(14):5329–5338

    CAS  PubMed  Google Scholar 

  • Nakazawa T, Watabe AM, Tezuka T, Yoshida Y, Yokoyama K, Umemori H, Inoue A, Okabe S, Manabe T, Yamamoto T (2003) p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling. Mol Biol Cell 14(7):2921–2934. doi:10.1091/mbc.E02-09-0623

    CAS  PubMed Central  PubMed  Google Scholar 

  • Newey SE, Velamoor V, Govek EE, Van Aelst L (2005) Rho GTPases, dendritic structure, and mental retardation. J Neurobiol 64(1):58–74. doi:10.1002/neu.20153

    CAS  PubMed  Google Scholar 

  • Newpher TM, Ehlers MD (2009) Spine microdomains for postsynaptic signaling and plasticity. Trends Cell Biol 19(5):218–227. doi:10.1016/j.tcb.2009.02.004

    PubMed  Google Scholar 

  • Oh D, Han S, Seo J, Lee JR, Choi J, Groffen J, Kim K, Cho YS, Choi HS, Shin H, Woo J, Won H, Park SK, Kim SY, Jo J, Whitcomb DJ, Cho K, Kim H, Bae YC, Heisterkamp N, Choi SY, Kim E (2010) Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins. J Neurosci 30(42):14134–14144. doi:10.1523/JNEUROSCI.1711-10.2010

    CAS  PubMed  Google Scholar 

  • Ohi K, Hashimoto R, Nakazawa T, Okada T, Yasuda Y, Yamamori H, Fukumoto M, Umeda-Yano S, Iwase M, Kazui H, Yamamoto T, Kano M, Takeda M (2012) The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits. PLoS One 7(4):e35696. doi:10.1371/journal.pone.0035696

    CAS  PubMed Central  PubMed  Google Scholar 

  • Okabe T, Nakamura T, Nishimura YN, Kohu K, Ohwada S, Morishita Y, Akiyama T (2003) RICS, a novel GTPase-activating protein for Cdc42 and Rac1, is involved in the beta-catenin-N-cadherin and N-methyl-D-aspartate receptor signaling. J Biol Chem 278(11):9920–9927. doi:10.1074/jbc.M208872200

    CAS  PubMed  Google Scholar 

  • Okada H, Uezu A, Mason FM, Soderblom EJ, Moseley MA 3rd, Soderling SH (2011) SH3 domain-based phototrapping in living cells reveals Rho family GAP signaling complexes. Sci Signal 4 (201):rs13. doi:10.1126/scisignal.2002189

  • Otomo T, Otomo C, Tomchick DR, Machius M, Rosen MK (2005) Structural basis of Rho GTPase-mediated activation of the formin mDia1. Mol Cell 18(3):273–281. doi:10.1016/j.molcel.2005.04.002

    CAS  PubMed  Google Scholar 

  • Padrick SB, Rosen MK (2010) Physical mechanisms of signal integration by WASP family proteins. Annu Rev Biochem 79:707–735. doi:10.1146/annurev.biochem.77.060407.135452

    CAS  PubMed Central  PubMed  Google Scholar 

  • Papadopoulos T, Soykan T (2011) The role of collybistin in gephyrin clustering at inhibitory synapses: facts and open questions. Front Cell Neurosci 5:11. doi:10.3389/fncel.2011.00011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Papadopoulos T, Korte M, Eulenburg V, Kubota H, Retiounskaia M, Harvey RJ, Harvey K, O'Sullivan GA, Laube B, Hulsmann S, Geiger JR, Betz H (2007) Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice. EMBO J 26(17):3888–3899. doi:10.1038/sj.emboj.7601819

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paterson HF, Self AJ, Garrett MD, Just I, Aktories K, Hall A (1990) Microinjection of recombinant p21rho induces rapid changes in cell morphology. J Cell Biol 111(3):1001–1007

    CAS  PubMed  Google Scholar 

  • Pawson CT, Scott JD (2010) Signal integration through blending, bolstering and bifurcating of intracellular information. Nat Struct Mol Biol 17(6):653–658. doi:10.1038/nsmb.1843

    CAS  PubMed Central  PubMed  Google Scholar 

  • Penzes P, Jones KA (2008) Dendritic spine dynamics–a key role for kalirin-7. Trends Neurosci 31(8):419–427. doi:10.1016/j.tins.2008.06.001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Philip N, Chabrol B, Lossi AM, Cardoso C, Guerrini R, Dobyns WB, Raybaud C, Villard L (2003) Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia. J Med Genet 40(6):441–446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pollitt AY, Insall RH (2009) WASP and SCAR/WAVE proteins: the drivers of actin assembly. J Cell Sci 122(Pt 15):2575–2578. doi:10.1242/jcs.023879

    CAS  PubMed Central  PubMed  Google Scholar 

  • Poulopoulos A, Aramuni G, Meyer G, Soykan T, Hoon M, Papadopoulos T, Zhang M, Paarmann I, Fuchs C, Harvey K, Jedlicka P, Schwarzacher SW, Betz H, Harvey RJ, Brose N, Zhang W, Varoqueaux F (2009) Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron 63(5):628–642. doi:10.1016/j.neuron.2009.08.023

    CAS  PubMed  Google Scholar 

  • Pucharcos C, Fuentes JJ, Casas C, de la Luna S, Alcantara S, Arbones ML, Soriano E, Estivill X, Pritchard M (1999) Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome. Eur J Hum Genet 7(6):704–712. doi:10.1038/sj.ejhg.5200356

    CAS  PubMed  Google Scholar 

  • Reddy-Alla S, Schmitt B, Birkenfeld J, Eulenburg V, Dutertre S, Bohringer C, Gotz M, Betz H, Papadopoulos T (2010) PH-domain-driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering. Eur J Neurosci 31(7):1173–1184. doi:10.1111/j.1460-9568.2010.07149.x

    PubMed  Google Scholar 

  • Rose R, Weyand M, Lammers M, Ishizaki T, Ahmadian MR, Wittinghofer A (2005) Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature 435(7041):513–518. doi:10.1038/nature03604

    CAS  PubMed  Google Scholar 

  • Rosenmund C, Westbrook GL (1993) Calcium-induced actin depolymerization reduces NMDA channel activity. Neuron 10(5):805–814

    CAS  PubMed  Google Scholar 

  • Ryan XP, Alldritt J, Svenningsson P, Allen PB, Wu GY, Nairn AC, Greengard P (2005) The Rho-specific GEF Lfc interacts with neurabin and spinophilin to regulate dendritic spine morphology. Neuron 47(1):85–100. doi:10.1016/j.neuron.2005.05.013

    CAS  PubMed  Google Scholar 

  • Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR (2008) Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron 57(1):94–107. doi:10.1016/j.neuron.2007.11.016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sanhueza M, Fernandez-Villalobos G, Stein IS, Kasumova G, Zhang P, Bayer KU, Otmakhov N, Hell JW, Lisman J (2011) Role of the CaMKII/NMDA receptor complex in the maintenance of synaptic strength. J Neurosci 31(25):9170–9178. doi:10.1523/JNEUROSCI.1250-11.2011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schell MJ, Erneux C, Irvine RF (2001) Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus. J Biol Chem 276(40):37537–37546. doi:10.1074/jbc.M104101200

    CAS  PubMed  Google Scholar 

  • Schermelleh L, Heintzmann R, Leonhardt H (2010) A guide to super-resolution fluorescence microscopy. J Cell Biol 190(2):165–175. doi:10.1083/jcb.201002018

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schlenker O, Rittinger K (2009) Structures of dimeric GIT1 and trimeric beta-PIX and implications for GIT-PIX complex assembly. J Mol Biol 386(2):280–289. doi:10.1016/j.jmb.2008.12.050

    CAS  PubMed  Google Scholar 

  • Schmalzigaug R, Rodriguiz RM, Bonner PE, Davidson CE, Wetsel WC, Premont RT (2009) Impaired fear response in mice lacking GIT1. Neurosci Lett 458(2):79–83. doi:10.1016/j.neulet.2009.04.037

    CAS  PubMed Central  PubMed  Google Scholar 

  • Settleman J (2003) A memory GAP. Trends Neurosci 26(6):285–287. doi:10.1016/S0166-2236(03)00103-6

    CAS  PubMed  Google Scholar 

  • Sfakianos MK, Eisman A, Gourley SL, Bradley WD, Scheetz AJ, Settleman J, Taylor JR, Greer CA, Williamson A, Koleske AJ (2007) Inhibition of Rho via Arg and p190RhoGAP in the postnatal mouse hippocampus regulates dendritic spine maturation, synapse and dendrite stability, and behavior. J Neurosci 27(41):10982–10992. doi:10.1523/JNEUROSCI.0793-07.2007

    CAS  PubMed  Google Scholar 

  • Sheffler-Collins SI, Dalva MB (2012) EphBs: an integral link between synaptic function and synaptopathies. Trends Neurosci 35(5):293–304. doi:10.1016/j.tins.2012.03.003

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shibata H, Mukai H, Inagaki Y, Homma Y, Kimura K, Kaibuchi K, Narumiya S, Ono Y (1996) Characterization of the interaction between RhoA and the amino-terminal region of PKN. FEBS Lett 385(3):221–224

    CAS  PubMed  Google Scholar 

  • Shimojima K, Sugawara M, Shichiji M, Mukaida S, Takayama R, Imai K, Yamamoto T (2011) Loss-of-function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy. J Hum Genet 56(8):561–565. doi:10.1038/jhg.2011.58

    CAS  PubMed  Google Scholar 

  • Snyder MA, Gao WJ (2013) NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front Cell Neurosci 7:31. doi:10.3389/fncel.2013.00031

    CAS  PubMed Central  PubMed  Google Scholar 

  • Soderling SH, Binns KL, Wayman GA, Davee SM, Ong SH, Pawson T, Scott JD (2002) The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. Nat Cell Biol 4(12):970–975. doi:10.1038/ncb886

    CAS  PubMed  Google Scholar 

  • Soderling SH, Langeberg LK, Soderling JA, Davee SM, Simerly R, Raber J, Scott JD (2003) Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc Natl Acad Sci U S A 100(4):1723–1728. doi:10.1073/pnas.0438033100

    CAS  PubMed Central  PubMed  Google Scholar 

  • Soderling SH, Guire ES, Kaech S, White J, Zhang F, Schutz K, Langeberg LK, Banker G, Raber J, Scott JD (2007) A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J Neurosci 27(2):355–365. doi:10.1523/JNEUROSCI.3209-06.2006

    CAS  PubMed Central  PubMed  Google Scholar 

  • St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G, Gosden C, Evans HJ (1990) Association within a family of a balanced autosomal translocation with major mental illness. Lancet 336(8706):13–16

    CAS  PubMed  Google Scholar 

  • Sudhof TC, Malenka RC (2008) Understanding synapses: past, present, and future. Neuron 60(3):469–476. doi:10.1016/j.neuron.2008.10.011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sun Y, Bamji SX (2011) beta-Pix modulates actin-mediated recruitment of synaptic vesicles to synapses. J Neurosci 31(47):17123–17133. doi:10.1523/JNEUROSCI.2359-11.2011

    CAS  PubMed  Google Scholar 

  • Tada T, Sheng M (2006) Molecular mechanisms of dendritic spine morphogenesis. Curr Opin Neurobiol 16(1):95–101. doi:10.1016/j.conb.2005.12.001

    CAS  PubMed  Google Scholar 

  • Tahirovic S, Bradke F (2009) Neuronal polarity. Cold Spring Harb Perspect Biol 1(3):a001644. doi:10.1101/cshperspect.a001644

    PubMed Central  PubMed  Google Scholar 

  • Takasu MA, Dalva MB, Zigmond RE, Greenberg ME (2002) Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295(5554):491–495. doi:10.1126/science.1065983

    CAS  PubMed  Google Scholar 

  • Tashiro A, Minden A, Yuste R (2000) Regulation of dendritic spine morphology by the rho family of small GTPases: antagonistic roles of Rac and Rho. Cereb Cortex 10(10):927–938

    CAS  PubMed  Google Scholar 

  • Thomas S, Ritter B, Verbich D, Sanson C, Bourbonniere L, McKinney RA, McPherson PS (2009) Intersectin regulates dendritic spine development and somatodendritic endocytosis but not synaptic vesicle recycling in hippocampal neurons. J Biol Chem 284(18):12410–12419. doi:10.1074/jbc.M809746200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tolias KF, Bikoff JB, Burette A, Paradis S, Harrar D, Tavazoie S, Weinberg RJ, Greenberg ME (2005) The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines. Neuron 45(4):525–538. doi:10.1016/j.neuron.2005.01.024

    CAS  PubMed  Google Scholar 

  • Tolias KF, Duman JG, Um K (2011) Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog Neurobiol 94(2):133–148. doi:10.1016/j.pneurobio.2011.04.011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Triller A, Choquet D (2008) New concepts in synaptic biology derived from single-molecule imaging. Neuron 59(3):359–374. doi:10.1016/j.neuron.2008.06.022

    CAS  PubMed  Google Scholar 

  • Tyagarajan SK, Ghosh H, Harvey K, Fritschy JM (2011) Collybistin splice variants differentially interact with gephyrin and Cdc42 to regulate gephyrin clustering at GABAergic synapses. J Cell Sci 124(Pt 16):2786–2796. doi:10.1242/jcs.086199

    CAS  PubMed Central  PubMed  Google Scholar 

  • Van Aelst L, D'Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11(18):2295–2322

    PubMed  Google Scholar 

  • van Bokhoven H (2011) Genetic and epigenetic networks in intellectual disabilities. Annu Rev Genet 45:81–104. doi:10.1146/annurev-genet-110410-132512

    PubMed  Google Scholar 

  • van Galen EJ, Ramakers GJ (2005) Rho proteins, mental retardation and the neurobiological basis of intelligence. Prog Brain Res 147:295–317. doi:10.1016/S0079-6123(04)47022-8

    PubMed  Google Scholar 

  • Waltereit R, Leimer U, von Bohlen Und Halbach O, Panke J, Holter SM, Garrett L, Wittig K, Schneider M, Schmitt C, Calzada-Wack J, Neff F, Becker L, Prehn C, Kutscherjawy S, Endris V, Bacon C, Fuchs H, Gailus-Durner V, Berger S, Schonig K, Adamski J, Klopstock T, Esposito I, Wurst W, de Angelis MH, Rappold G, Wieland T, Bartsch D (2012) Srgap3-/- mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes. FASEB J. doi:10.1096/fj.11-202317

    PubMed  Google Scholar 

  • Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ (2008) N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J Biol Chem 283(23):15912–15920. doi:10.1074/jbc.M801555200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson KA, Lee Y, Long R, Hermetz K, Rudd MK, Miller R, Rapoport JL, Addington AM (2011) A Novel Microduplication in the Neurodevelopmental Gene SRGAP3 That Segregates with Psychotic Ilness in the Family of a COS Proband. Case Rep Genet 2011:585893

    Google Scholar 

  • Windhorst S, Blechner C, Lin HY, Elling C, Nalaskowski M, Kirchberger T, Guse AH, Mayr GW (2008) Ins(1,4,5)P3 3-kinase-A overexpression induces cytoskeletal reorganization via a kinase-independent mechanism. Biochem J 414(3):407–417. doi:10.1042/BJ20080630

    CAS  PubMed  Google Scholar 

  • Won H, Mah W, Kim E, Kim JW, Hahm EK, Kim MH, Cho S, Kim J, Jang H, Cho SC, Kim BN, Shin MS, Seo J, Jeong J, Choi SY, Kim D, Kang C (2011) GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice. Nat Med 17(5):566–572. doi:10.1038/nm.2330

    CAS  PubMed  Google Scholar 

  • Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM (2009) A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461(7260):104–108. doi:10.1038/nature08241

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (1997) Competitive binding of alpha-actinin and calmodulin to the NMDA receptor. Nature 385(6615):439–442. doi:10.1038/385439a0

    CAS  PubMed  Google Scholar 

  • Zamanian JL, Kelly RB (2003) Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis. Mol Biol Cell 14(4):1624–1637. doi:10.1091/mbc.E02-08-0494

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zanni G, Saillour Y, Nagara M, Billuart P, Castelnau L, Moraine C, Faivre L, Bertini E, Durr A, Guichet A, Rodriguez D, des Portes V, Beldjord C, Chelly J (2005) Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia. Neurology 65(9):1364–1369. doi:10.1212/01.wnl.0000182813.94713.ee

    CAS  PubMed  Google Scholar 

  • Zhang H, Macara IG (2008) The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Dev Cell 14(2):216–226. doi:10.1016/j.devcel.2007.11.020

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Jim Duffy for his help with the graphic art of Fig. 17.1. We apologize to colleagues we did not cite due to space limitations. L.V.A. is supported by grants from the NIH (R01 MH082808 and R01 NS082266) and S.H.S by NIH (2R56NS059957-06).

The authors declare that they have no conflict of interest and that there are no competing financial interests.

Author information

Authors and Affiliations

  1. Departments of Cell Biology and Neurobiology, Duke University Medical School, Durham, NC, USA

    Scott H. Soderling

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    Linda Van Aelst

Authors
  1. Scott H. Soderling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda Van Aelst
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Scott H. Soderling or Linda Van Aelst .

Editor information

Editors and Affiliations

  1. Max-Planck-Institute of Molecular Physiology, Dortmund, Nordrhein-Westfalen, Germany

    Alfred Wittinghofer

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Soderling, S.H., Van Aelst, L. (2014). Principles Driving the Spatial Organization of Rho GTPase Signaling at Synapses. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1806-1_17

Download citation

Publish with us

Policies and ethics

Search

Navigation