The formation of synapses and the proper construction of neural circuits depend on signaling pathways that regulate cytoskeletal structure and dynamics. After the mutual recognition of a growing axon and its target, multiple signaling pathways are activated that regulate cytoskeletal dynamics to determine the morphology and strength of the connection. By analyzing Drosophila mutations in the cytoplasmic FMRP interacting protein Cyfip, we demonstrate that this component of the WAVE complex inhibits the assembly of filamentous actin (F-actin) and thereby regulates key aspects of synaptogenesis. Cyfip regulates the distribution of F-actin filaments in presynaptic neuromuscular junction (NMJ) terminals. At cyfip mutant NMJs, F-actin assembly was accelerated, resulting in shorter NMJs, more numerous satellite boutons, and reduced quantal content. Increased synaptic vesicle size and failure to maintain excitatory junctional potential amplitudes under high-frequency stimulation in cyfip mutants indicated an endocytic defect. cyfip mutants exhibited upregulated bone morphogenetic protein (BMP) signaling, a major growth-promoting pathway known to be attenuated by endocytosis at the Drosophila NMJ. We propose that Cyfip regulates synapse development and endocytosis by inhibiting actin assembly.
Vyšlo v časopise: Regulates Synaptic Development and Endocytosis by Suppressing Filamentous Actin Assembly. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003450 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003450
1. CollinsCA, DiAntonioA (2007) Synaptic development: insights from Drosophila. Curr Opin Neurobiol 17 : 35–42.
2. GiagtzoglouN, LyCV, BellenHJ (2009) Cell adhesion, the backbone of the synapse: “vertebrate” and “invertebrate” perspectives. Cold Spring Harb Perspect Biol 1: a003079.
3. PackardM, MathewD, BudnikV (2003) Wnts and TGF beta in synaptogenesis: old friends signalling at new places. Nat Rev Neurosci 4 : 113–120.
4. BallRW, Warren-PaquinM, TsurudomeK, LiaoEH, ElazzouziF, et al. (2010) Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons. Neuron 66 : 536–549.
5. DillonC, GodaY (2005) The actin cytoskeleton: integrating form and function at the synapse. Annu Rev Neurosci 28 : 25–55.
6. PielageJ, BulatV, ZucheroJB, FetterRD, DavisGW (2011) Hts/Adducin controls synaptic elaboration and elimination. Neuron 69 : 1114–1131.
7. O'Connor-GilesKM, HoLL, GanetzkyB (2008) Nervous wreck interacts with thickveins and the endocytic machinery to attenuate retrograde BMP signaling during synaptic growth. Neuron 58 : 507–518.
8. RodalAA, Motola-BarnesRN, LittletonJT (2008) Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth. J Neurosci 28 : 8316–8325.
9. KhuongTM, HabetsRL, SlabbaertJR, VerstrekenP (2010) WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling. Proc Natl Acad Sci U S A 107 : 17379–17384.
10. PielageJ, FetterRD, DavisGW (2005) Presynaptic spectrin is essential for synapse stabilization. Curr Biol 15 : 918–928.
11. RichardsDA, RizzoliSO, BetzWJ (2004) Effects of wortmannin and latrunculin A on slow endocytosis at the frog neuromuscular junction. J Physiol 557 : 77–91.
12. ShupliakovO, BloomO, GustafssonJS, KjaerulffO, LowP, et al. (2002) Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton. Proc Natl Acad Sci U S A 99 : 14476–14481.
13. HussainNK, JennaS, GlogauerM, QuinnCC, WasiakS, et al. (2001) Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3 : 927–932.
14. NunesP, HainesN, KuppuswamyV, FleetDJ, StewartBA (2006) Synaptic vesicle mobility and presynaptic F-actin are disrupted in a N-ethylmaleimide-sensitive factor allele of Drosophila. Mol Biol Cell 17 : 4709–4719.
15. KohTW, VerstrekenP, BellenHJ (2004) Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis. Neuron 43 : 193–205.
16. MarieB, SweeneyST, PoskanzerKE, RoosJ, KellyRB, et al. (2004) Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth. Neuron 43 : 207–219.
17. WangD, ZhangL, ZhaoG, WahlstromG, HeinoTI, et al. (2010) Drosophila twinfilin is required for cell migration and synaptic endocytosis. J Cell Sci 123 : 1546–1556.
18. ChenZ, BorekD, PadrickSB, GomezTS, MetlagelZ, et al. (2010) Structure and control of the actin regulatory WAVE complex. Nature 468 : 533–538.
19. EdenS, RohatgiR, PodtelejnikovAV, MannM, KirschnerMW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418 : 790–793.
20. GautreauA, HoHY, LiJ, SteenH, GygiSP, et al. (2004) Purification and architecture of the ubiquitous Wave complex. Proc Natl Acad Sci U S A 101 : 4379–4383.
21. IsmailAM, PadrickSB, ChenB, UmetaniJ, RosenMK (2009) The WAVE regulatory complex is inhibited. Nat Struct Mol Biol 16 : 561–563.
22. KobayashiK, KurodaS, FukataM, NakamuraT, NagaseT, et al. (1998) p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase. J Biol Chem 273 : 291–295.
23. LebensohnAM, KirschnerMW (2009) Activation of the WAVE complex by coincident signals controls actin assembly. Mol Cell 36 : 512–524.
24. SchenckA, BardoniB, LangmannC, HardenN, MandelJL, et al. (2003) CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein. Neuron 38 : 887–898.
25. CoyleIP, KohYH, LeeWC, SlindJ, FergestadT, et al. (2004) Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila. Neuron 41 : 521–534.
26. DickmanDK, LuZ, MeinertzhagenIA, SchwarzTL (2006) Altered synaptic development and active zone spacing in endocytosis mutants. Curr Biol 16 : 591–598.
27. KohTW, KorolchukVI, WairkarYP, JiaoW, EvergrenE, et al. (2007) Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J Cell Biol 178 : 309–322.
28. VerstrekenP, OhyamaT, HaueterC, HabetsRL, LinYQ, et al. (2009) Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. Neuron 63 : 203–215.
29. YaoCK, LinYQ, LyCV, OhyamaT, HaueterCM, et al. (2009) A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. Cell 138 : 947–960.
30. ZhangB, KohYH, BecksteadRB, BudnikV, GanetzkyB, et al. (1998) Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. Neuron 21 : 1465–1475.
31. DickmanDK, HorneJA, MeinertzhagenIA, SchwarzTL (2005) A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin. Cell 123 : 521–533.
32. SweeneyST, DavisGW (2002) Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation. Neuron 36 : 403–416.
33. ChiharaT, KatoK, TaniguchiM, NgJ, HayashiS (2003) Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila. Development 130 : 1419–1428.
34. EdwardsKA, DemskyM, MontagueRA, WeymouthN, KiehartDP (1997) GFP-moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila. Dev Biol 191 : 103–117.
35. LeeCW, HanJ, BamburgJR, HanL, LynnR, et al. (2009) Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nat Neurosci 12 : 848–856.
36. BubbMR, SenderowiczAM, SausvilleEA, DuncanKL, KornED (1994) Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. J Biol Chem 269 : 14869–14871.
37. ChuD, PanH, WanP, WuJ, LuoJ, et al. (2012) AIP1 acts with cofilin to control actin dynamics during epithelial morphogenesis. Development 139 : 3561–3571.
38. WolffT, ReadyDF (1991) The beginning of pattern formation in the Drosophila compound eye: the morphogenetic furrow and the second mitotic wave. Development 113 : 841–850.
39. BogdanS, GreweO, StrunkM, MertensA, KlambtC (2004) Sra-1 interacts with Kette and Wasp and is required for neuronal and bristle development in Drosophila. Development 131 : 3981–3989.
40. KundaP, CraigG, DominguezV, BaumB (2003) Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions. Curr Biol 13 : 1867–1875.
41. SchenckA, QurashiA, CarreraP, BardoniB, DieboldC, et al. (2004) WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity. Dev Biol 274 : 260–270.
42. BogdanS, KlambtC (2003) Kette regulates actin dynamics and genetically interacts with Wave and Wasp. Development 130 : 4427–4437.
43. NapoliI, MercaldoV, BoylPP, EleuteriB, ZalfaF, et al. (2008) The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134 : 1042–1054.
44. ZhangYQ, BaileyAM, MatthiesHJ, RendenRB, SmithMA, et al. (2001) Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107 : 591–603.
45. HeerssenH, FetterRD, DavisGW (2008) Clathrin dependence of synaptic-vesicle formation at the Drosophila neuromuscular junction. Curr Biol 18 : 401–409.
46. CingolaniLA, GodaY (2008) Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 9 : 344–356.
47. FergusonSM, RaimondiA, ParadiseS, ShenH, MesakiK, et al. (2009) Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell 17 : 811–822.
48. KaksonenM, ToretCP, DrubinDG (2006) Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 7 : 404–414.
49. LiuZ, HuangY, ZhangY, ChenD, ZhangYQ (2011) Drosophila Acyl-CoA synthetase long-chain family member 4 regulates axonal transport of synaptic vesicles and is required for synaptic development and transmission. J Neurosci 31 : 2052–2063.
50. MartinAR (1955) A further study of the statistical composition on the end-plate potential. J Physiol 130 : 114–122.
51. AxelrodD, KoppelDE, SchlessingerJ, ElsonE, WebbWW (1976) Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J 16 : 1055–1069.
52. HotulainenP, LlanoO, SmirnovS, TanhuanpaaK, FaixJ, et al. (2009) Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol 185 : 323–339.
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