Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion

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The formation of sterotyped neuronal connections during embryonic development is essential for animal survival and behavior. In particular, establishing proper connectivity at the midline is critical for the orchestration of rhythmic behaviors. Conserved genetic programs that instruct axon guidance at the midline have been characterized in multiple model systems, but the signaling mechanisms underlying axon guidance are not well understood. Slits and Robos comprise conserved families of axon guidance cues and receptors that control midline guidance by preventing inappropriate midline crossing. Here, we identify a novel mechanism that is required for Robo receptor activation and Robo-dependent axon repulsion in vivo. Using a combination of molecular genetic and cell biological approaches, we define a role for Slit-dependent trafficking of Robo from the plasma membrane to the early and late endosomes that contributes to Robo activation and signaling. In previous work, endocytic trafficking has been shown to modulate axon guidance responses by regulating surface levels of guidance receptors. In contrast, our observations indicate that endocytosis of the Robo receptor itself is required for receptor activation and precedes the recruitment of a key downstream signaling effector to the Robo receptor cytoplasmic domain.

Vyšlo v časopise: Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005402
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005402

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1. Brose K, Bland KS, Wang KH, Arnott D, Henzel W, et al. (1999) Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96: 795–806. 10102268

2. Kidd T, Bland KS, Goodman CS (1999) Slit is the midline repellent for the robo receptor in Drosophila. Cell 96: 785–794. 10102267

3. Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, et al. (1998a) Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92: 205–215.

4. Wang KH, Brose K, Arnott D, Kidd T, Goodman CS, et al. (1999) Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching. Cell 96: 771–784. 10102266

5. Anitha A, Nakamura K, Yamada K, Suda S, Thanseem I, et al. (2008) Genetic analyses of roundabout (ROBO) axon guidance receptors in autism. Am J Med Genet B Neuropsychiatr Genet 147B: 1019–1027. doi: 10.1002/ajmg.b.30697 18270976

6. Potkin SG, Turner JA, Guffanti G, Lakatos A, Fallon JH, et al. (2009) A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophr Bull 35: 96–108. doi: 10.1093/schbul/sbn155 19023125

7. Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, et al. (2007) A structural basis for reading fluency: white matter defects in a genetic brain malformation. Neurology 69: 2146–2154. 18056578

8. Seeger M, Tear G, Ferres-Marco D, Goodman CS (1993) Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 10: 409–426. 8461134

9. Shu T, Richards LJ (2001) Cortical axon guidance by the glial wedge during the development of the corpus callosum. J Neurosci 21: 2749–2758. 11306627

10. Ma L, Tessier-Lavigne M (2007) Dual branch-promoting and branch-repelling actions of Slit/Robo signaling on peripheral and central branches of developing sensory axons. J Neurosci 27: 6843–6851. 17581972

11. Johnson KG, Ghose A, Epstein E, Lincecum J, O'Connor MB, et al. (2004) Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance. Curr Biol 14: 499–504. 15043815

12. Murray MJ, Whitington PM (1999) Effects of roundabout on growth cone dynamics, filopodial length, and growth cone morphology at the midline and throughout the neuropile. J Neurosci 19: 7901–7912. 10479692

13. Hutson LD, Chien CB (2002) Pathfinding and error correction by retinal axons: the role of astray/robo2. Neuron 33: 205–217. 11804569

14. Cowan CW, Shao YR, Sahin M, Shamah SM, Lin MZ, et al. (2005) Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 46: 205–217. 15848800

15. Hattori M, Osterfield M, Flanagan JG (2000) Regulated cleavage of a contact-mediated axon repellent. Science 289: 1360–1365. 10958785

16. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, et al. (2005) Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123: 291–304. 16239146

17. Lin KT, Sloniowski S, Ethell DW, Ethell IM (2008) Ephrin-B2 induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion. J Biol Chem.

18. Marston DJ, Dickinson S, Nobes CD (2003) Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion. Nat Cell Biol 5: 879–888. 12973357

19. Zimmer M, Palmer A, Kohler J, Klein R (2003) EphB-ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion. Nat Cell Biol 5: 869–878. 12973358

20. Jurney WM, Gallo G, Letourneau PC, McLoon SC (2002) Rac1-mediated endocytosis during ephrin-A2- and semaphorin 3A-induced growth cone collapse. J Neurosci 22: 6019–6028. 12122063

21. Piper M, Anderson R, Dwivedy A, Weinl C, van Horck F, et al. (2006) Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones. Neuron 49: 215–228. 16423696

22. Hines JH, Abu-Rub M, Henley JR (2010) Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG. Nat Neurosci 13: 829–837. doi: 10.1038/nn.2554 20512137

23. Onishi K, Shafer B, Lo C, Tissir F, Goffinet AM, et al. (2013) Antagonistic functions of Dishevelleds regulate Frizzled3 endocytosis via filopodia tips in Wnt-mediated growth cone guidance. J Neurosci 33: 19071–19085. doi: 10.1523/JNEUROSCI.2800-13.2013 24305805

24. Tojima T, Itofusa R, Kamiguchi H (2010) Asymmetric clathrin-mediated endocytosis drives repulsive growth cone guidance. Neuron 66: 370–377. doi: 10.1016/j.neuron.2010.04.007 20471350

25. Bartoe JL, McKenna WL, Quan TK, Stafford BK, Moore JA, et al. (2006) Protein interacting with C-kinase 1/protein kinase Calpha-mediated endocytosis converts netrin-1-mediated repulsion to attraction. J Neurosci 26: 3192–3205. 16554470

26. O'Donnell M, Chance RK, Bashaw GJ (2009) Axon growth and guidance: receptor regulation and signal transduction. Annu Rev Neurosci 32: 383–412. doi: 10.1146/annurev.neuro.051508.135614 19400716

27. Williams ME, Wu SC, McKenna WL, Hinck L (2003) Surface expression of the netrin receptor UNC5H1 is regulated through a protein kinase C-interacting protein/protein kinase-dependent mechanism. J Neurosci 23: 11279–11288. 14672991

28. Keleman K, Rajagopalan S, Cleppien D, Teis D, Paiha K, et al. (2002) Comm sorts robo to control axon guidance at the Drosophila midline. Cell 110: 415–427. 12202032

29. Keleman K, Ribeiro C, Dickson BJ (2005) Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Nat Neurosci 8: 156–163. 15657595

30. Yoo S, Kim Y, Noh H, Lee H, Park E, et al. (2011) Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map. EMBO J 30: 1593–1607. doi: 10.1038/emboj.2011.44 21343910

31. Coleman HA, Labrador JP, Chance RK, Bashaw GJ (2010) The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline. Development 137: 2417–2426. doi: 10.1242/dev.047993 20570941

32. Fan X, Labrador JP, Hing H, Bashaw GJ (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. 14527437

33. Hsouna A, Kim YS, VanBerkum MF (2003) Abelson tyrosine kinase is required to transduce midline repulsive cues. J Neurobiol 57: 15–30. 12973825

34. Hu H, Li M, Labrador JP, McEwen J, Lai EC, et al. (2005) Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion. Proc Natl Acad Sci U S A 102: 4613–4618. 15755809

35. Gonzalez-Gaitan M, Jackle H (1997) Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell 88: 767–776. 9118220

36. Guichet A, Wucherpfennig T, Dudu V, Etter S, Wilsch-Brauniger M, et al. (2002) Essential role of endophilin A in synaptic vesicle budding at the Drosophila neuromuscular junction. EMBO J 21: 1661–1672. 11927550

37. Moline MM, Southern C, Bejsovec A (1999) Directionality of wingless protein transport influences epidermal patterning in the Drosophila embryo. Development 126: 4375–4384. 10477304

38. van der Bliek AM, Redelmeier TE, Damke H, Tisdale EJ, Meyerowitz EM, et al. (1993) Mutations in human dynamin block an intermediate stage in coated vesicle formation. J Cell Biol 122: 553–563. 8101525

39. O'Donnell MP, Bashaw GJ (2013) Src Inhibits Midline Axon Crossing Independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) Receptor Tyrosine Phosphorylation. J Neurosci 33: 305–314. doi: 10.1523/JNEUROSCI.2756-12.2013 23283343

40. Ohno H, Stewart J, Fournier MC, Bosshart H, Rhee I, et al. (1995) Interaction of tyrosine-based sorting signals with clathrin-associated proteins. Science 269: 1872–1875. 7569928

41. Sorkin A, Mazzotti M, Sorkina T, Scotto L, Beguinot L (1996) Epidermal growth factor receptor interaction with clathrin adaptors is mediated by the Tyr974-containing internalization motif. J Biol Chem 271: 13377–13384. 8662849

42. Wisco D, Anderson ED, Chang MC, Norden C, Boiko T, et al. (2003) Uncovering multiple axonal targeting pathways in hippocampal neurons. J Cell Biol 162: 1317–1328. 14517209

43. Fukuhara N, Howitt JA, Hussain SA, Hohenester E (2008) Structural and functional analysis of slit and heparin binding to immunoglobulin-like domains 1 and 2 of Drosophila Robo. J Biol Chem 283: 16226–16234. doi: 10.1074/jbc.M800688200 18359766

44. Howitt JA, Clout NJ, Hohenester E (2004) Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. Embo J 23: 4406–4412. 15496984

45. Liu Z, Patel K, Schmidt H, Andrews W, Pini A, et al. (2004) Extracellular Ig domains 1 and 2 of Robo are important for ligand (Slit) binding. Mol Cell Neurosci 26: 232–240. 15207848

46. Bashaw GJ, Goodman CS (1999) Chimeric axon guidance receptors: the cytoplasmic domains of slit and netrin receptors specify attraction versus repulsion. Cell 97: 917–926. 10399919

47. Bashaw GJ, Kidd T, Murray D, Pawson T, Goodman CS (2000) Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell 101: 703–715. 10892742

48. Yang L, Bashaw GJ (2006) Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline. Neuron 52: 595–607. 17114045

49. Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, et al. (2006) Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10: 839–850. 16740485

50. Slovakova J, Speicher S, Sanchez-Soriano N, Prokop A, Carmena A (2012) The actin-binding protein Canoe/AF-6 forms a complex with Robo and is required for Slit-Robo signaling during axon pathfinding at the CNS midline. J Neurosci 32: 10035–10044. doi: 10.1523/JNEUROSCI.6342-11.2012 22815517

51. Seto ES, Bellen HJ (2006) Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol 173: 95–106. 16606693

52. Vaccari T, Lu H, Kanwar R, Fortini ME, Bilder D (2008) Endosomal entry regulates Notch receptor activation in Drosophila melanogaster. J Cell Biol 180: 755–762. doi: 10.1083/jcb.200708127 18299346

53. Jekely G, Sung HH, Luque CM, Rorth P (2005) Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Dev Cell 9: 197–207. 16054027

54. Lanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, et al. (2010) VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell 18: 713–724. doi: 10.1016/j.devcel.2010.02.016 20434959

55. Palamidessi A, Frittoli E, Garré M, Faretta M, Mione M, et al. (2008) Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134: 135–147. doi: 10.1016/j.cell.2008.05.034 18614017

56. Slessareva JE, Routt SM, Temple B, Bankaitis VA, Dohlman HG (2006) Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome. Cell 126: 191–203. 16839886

57. Teis D, Taub N, Kurzbauer R, Hilber D, de Araujo ME, et al. (2006) p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis. J Cell Biol 175: 861–868. 17178906

58. Sorkin A, von Zastrow M (2009) Endocytosis and signalling: intertwining molecular networks. Nat Rev Mol Cell Biol 10: 609–622. doi: 10.1038/nrm2748 19696798

59. Gupta GD, Swetha MG, Kumari S, Lakshminarayan R, Dey G, et al. (2009) Analysis of endocytic pathways in Drosophila cells reveals a conserved role for GBF1 in internalization via GEECs. PLoS One 4: e6768. doi: 10.1371/journal.pone.0006768 19707569

60. Piper M, Salih S, Weinl C, Holt CE, Harris WA (2005) Endocytosis-dependent desensitization and protein synthesis-dependent resensitization in retinal growth cone adaptation. Nat Neurosci 8: 179–186. 15643427

61. Galperin E, Sorkin A (2003) Visualization of Rab5 activity in living cells by FRET microscopy and influence of plasma-membrane-targeted Rab5 on clathrin-dependent endocytosis. J Cell Sci 116: 4799–4810. 14600265

62. Das B, Shu X, Day GJ, Han J, Krishna UM, et al. (2000) Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding. J Biol Chem 275: 15074–15081. 10748082

63. Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L, et al. (1999) Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol 1: 249–252. 10559924

64. Li G, D'Souza-Schorey C, Barbieri MA, Roberts RL, Klippel A, et al. (1995) Evidence for phosphatidylinositol 3-kinase as a regulator of endocytosis via activation of Rab5. Proc Natl Acad Sci U S A 92: 10207–10211. 7479754

65. Ozdinler PH, Erzurumlu RS (2002) Slit2, a branching-arborization factor for sensory axons in the Mammalian CNS. J Neurosci 22: 4540–4549. 12040061

66. Whitford KL, Marillat V, Stein E, Goodman CS, Tessier-Lavigne M, et al. (2002) Regulation of cortical dendrite development by Slit-Robo interactions. Neuron 33: 47–61. 11779479

67. Lanier LM, Gates MA, Witke W, Menzies AS, Wehman AM, et al. (1999) Mena is required for neurulation and commissure formation. Neuron 22: 313–325. 10069337

68. Matusek T, Gombos R, Szecsenyi A, Sanchez-Soriano N, Czibula A, et al. (2008) Formin proteins of the DAAM subfamily play a role during axon growth. J Neurosci 28: 13310–13319. doi: 10.1523/JNEUROSCI.2727-08.2008 19052223

69. Kapfhammer JP, Raper JA (1987) Collapse of growth cone structure on contact with specific neurites in culture. J Neurosci 7: 201–212. 3543248

70. Falk J, Konopacki FA, Zivraj KH, Holt CE (2014) Rab5 and Rab4 regulate axon elongation in the Xenopus visual system. J Neurosci 34: 373–391. doi: 10.1523/JNEUROSCI.0876-13.2014 24403139

71. van Bergeijk P, Adrian M, Hoogenraad CC, Kapitein LC (2015) Optogenetic control of organelle transport and positioning. Nature 518: 111–114. doi: 10.1038/nature14128 25561173

72. Itofusa R, Kamiguchi H (2011) Polarizing membrane dynamics and adhesion for growth cone navigation. Mol Cell Neurosci 48: 332–338. doi: 10.1016/j.mcn.2011.03.007 21459144

73. Diefenbach TJ, Guthrie PB, Stier H, Billups B, Kater SB (1999) Membrane recycling in the neuronal growth cone revealed by FM1-43 labeling. J Neurosci 19: 9436–9444. 10531447

74. Kamiguchi H, Lemmon V (2000) Recycling of the cell adhesion molecule L1 in axonal growth cones. J Neurosci 20: 3676–3686. 10804209

75. Campbell DS, Holt CE (2001) Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation. Neuron 32: 1013–1026. 11754834