MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways

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Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone. A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 (lamellipodin). MIG-10 is thought to asymmetrically promote outgrowth by inducing actin polymerization. However, the mechanism that links MIG-10 to actin polymerization is not known. We have identified the actin regulatory protein ABI-1 as a partner for MIG-10 that can mediate its outgrowth-promoting activity. The SH3 domain of ABI-1 binds to MIG-10, and loss of function of either of these proteins causes similar axon guidance defects. Like MIG-10, ABI-1 functions in both the attractive UNC-6 (netrin) pathway and the repulsive SLT-1 (slit) pathway. Dosage sensitive genetic interactions indicate that MIG-10 functions with ABI-1 and WVE-1 to mediate axon guidance. Epistasis analysis reveals that ABI-1 and WVE-1 function downstream of MIG-10 to mediate its outgrowth-promoting activity. Moreover, experiments with cultured mammalian cells suggest that the interaction between MIG-10 and ABI-1 mediates a conserved mechanism that promotes formation of lamellipodia. Together, these observations suggest that MIG-10 interacts with ABI-1 and WVE-1 to mediate the UNC-6 and SLT-1 guidance pathways.

Vyšlo v časopise: MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways. PLoS Genet 8(11): e32767. doi:10.1371/journal.pgen.1003054
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003054

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Zdroje

1. Lai Wing SunK, CorreiaJP, KennedyTE (2011) Netrins: versatile extracellular cues with diverse functions. Development 138: 2153–2169.

2. KolodkinAL, Tessier-LavigneM (2010) Mechanisms and molecules of neuronal wiring: a primer. Cold Spring Harb Perspect Biol 3.

3. RaperJ, MasonC (2010) Cellular strategies of axonal pathfinding. Cold Spring Harb Perspect Biol 2: a001933.

4. ChedotalA, RichardsLJ (2010) Wiring the brain: the biology of neuronal guidance. Cold Spring Harb Perspect Biol 2: a001917.

5. O'DonnellM, ChanceRK, BashawGJ (2009) Axon growth and guidance: receptor regulation and signal transduction. Annu Rev Neurosci 32: 383–412.

6. BashawGJ, KleinR (2010) Signaling from axon guidance receptors. Cold Spring Harb Perspect Biol 2: a001941.

7. MarsickBM, FlynnKC, Santiago-MedinaM, BamburgJR, LetourneauPC (2010) Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1. Dev Neurobiol 70: 565–588.

8. NorrisAD, LundquistEA (2011) UNC-6/netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans. Development 138: 4433–4442.

9. O'ConnorTP, BentleyD (1993) Accumulation of actin in subsets of pioneer growth cone filopodia in response to neural and epithelial guidance cues in situ. J Cell Biol 123: 935–948.

10. DentEW, GuptonSL, GertlerFB (2011) The growth cone cytoskeleton in axon outgrowth and guidance. Cold Spring Harb Perspect Biol 3.

11. NorrisAD, DyerJO, LundquistEA (2009) The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans. Neural Dev 4: 38.

12. KorobovaF, SvitkinaT (2008) Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol Biol Cell 19: 1561–1574.

13. ShakirMA, JiangK, StruckhoffEC, DemarcoRS, PatelFB, et al. (2008) The Arp2/3 activators WAVE and WASP have distinct genetic interactions with Rac GTPases in Caenorhabditis elegans axon guidance. Genetics 179: 1957–1971.

14. ZallenJA, CohenY, HudsonAM, CooleyL, WieschausE, et al. (2002) SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila. J Cell Biol 156: 689–701.

15. AdlerCE, FetterRD, BargmannCI (2006) UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation. Nat Neurosci 9: 511–518.

16. ChangC, AdlerCE, KrauseM, ClarkSG, GertlerFB, et al. (2006) MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin. Curr Biol 16: 854–862.

17. QuinnCC, PfeilDS, ChenE, StovallEL, HardenMV, et al. (2006) UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin. Curr Biol 16: 845–853.

18. QuinnCC, PfeilDS, WadsworthWG (2008) CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin. Curr Biol 18: 808–813.

19. QuinnCC, WadsworthWG (2008) Axon guidance: asymmetric signaling orients polarized outgrowth. Trends Cell Biol 18: 597–603.

20. KrauseM, LeslieJD, StewartM, LafuenteEM, ValderramaF, et al. (2004) Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Dev Cell 7: 571–583.

21. InnocentiM, ZucconiA, DisanzaA, FrittoliE, ArecesLB, et al. (2004) Abi1 is essential for the formation and activation of a WAVE2 signalling complex. Nat Cell Biol 6: 319–327.

22. 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.

23. PatelFB, BernadskayaYY, ChenE, JobanputraA, PooladiZ, et al. (2008) The WAVE/SCAR complex promotes polarized cell movements and actin enrichment in epithelia during C. elegans embryogenesis. Dev Biol 324: 297–309.

24. RogersSL, WiedemannU, StuurmanN, ValeRD (2003) Molecular requirements for actin-based lamella formation in Drosophila S2 cells. J Cell Biol 162: 1079–1088.

25. SteffenA, RottnerK, EhingerJ, InnocentiM, ScitaG, et al. (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J 23: 749–759.

26. SotoMC, QadotaH, KasuyaK, InoueM, TsuboiD, et al. (2002) The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans. Genes & development 16: 620–632.

27. AlexanderM, ChanKK, ByrneAB, SelmanG, LeeT, et al. (2009) An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans. Development 136: 911–922.

28. McSheaMA, SchmidtKL, DubukeML, BaldigaCE, SullenderME, et al. (2012) Abelson interactor-1 (ABI-1) interacts with MRL adaptor protein MIG-10 and is required in guided cell migrations and process outgrowth in C.elegans. Dev Biol in press. doi: 10.1016/j.ydbio.2012.09.017.

29. StavoeAKH, NelsonJC, Martínez-VelázquezLA, KleinM, SamuelADT, et al. (2012) Synaptic Vesicle Clustering Requires a Distinct MIG-10/Lamellipodin Isoform and ABI-1 downstream from Netrin. Genes and Development 26: 2206–2221.

30. GitaiZ, YuTW, LundquistEA, Tessier-LavigneM, BargmannCI (2003) The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM. Neuron 37: 53–65.

31. YuTW, HaoJC, LimW, Tessier-LavigneM, BargmannCI (2002) Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci 5: 1147–1154.

32. SchmidtKL, Marcus-GueretN, AdeleyeA, WebberJ, BaillieD, et al. (2009) The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1. Development 136: 563–574.

33. BernadskayaYY, WallaceA, NguyenJ, MohlerWA, SotoMC (2012) UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph Polarize F-Actin during Embryonic Morphogenesis by Regulating the WAVE/SCAR Actin Nucleation Complex. PLoS Genet 8: e1002863 doi:10.1371/journal.pgen.1002863.

34. BourneHR, WeinerO (2002) A chemical compass. Nature 419: 21.

35. WeinerOD (2002) Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass. Curr Opin Cell Biol 14: 196–202.

36. PollardTD (2007) Regulation of actin filament assembly by Arp2/3 complex and formins. Annu Rev Biophys Biomol Struct 36: 451–477.

37. StradalT, CourtneyKD, RottnerK, HahneP, SmallJV, et al. (2001) The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia. Curr Biol 11: 891–895.

38. BashawGJ, KiddT, MurrayD, PawsonT, GoodmanCS (2000) Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell 101: 703–715.

39. FanX, LabradorJP, HingH, BashawGJ (2003) Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron 40: 113–127.

40. ForsthoefelDJ, LieblEC, KolodziejPA, SeegerMA (2005) The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila. Development 132: 1983–1994.

41. LebrandC, DentEW, StrasserGA, LanierLM, KrauseM, et al. (2004) Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1. Neuron 42: 37–49.

42. PicardM, PetrieRJ, Antoine-BertrandJ, Saint-Cyr-ProulxE, VillemureJF, et al. (2009) Spatial and temporal activation of the small GTPases RhoA and Rac1 by the netrin-1 receptor UNC5a during neurite outgrowth. Cell Signal 21: 1961–1973.

43. XiongH, MohlerWA, SotoMC (2011) The branched actin nucleator Arp2/3 promotes nuclear migrations and cell polarity in the C. elegans zygote. Dev Biol 357: 356–369.

44. XuY, RenXC, QuinnCC, WadsworthWG (2011) Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans. Genetics 189: 899–906.

45. QuinnCC, ChenE, KinjoTG, KellyG, BellAW, et al. (2003) TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicles in the growth cone. J Neurosci 23: 2815–2823.

46. ChenZ, BorekD, PadrickSB, GomezTS, MetlagelZ, et al. Structure and control of the actin regulatory WAVE complex. Nature 468: 533–538.