Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor - PubMed (original) (raw)

Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor

G J Bashaw et al. Cell. 2000.

Free article

Abstract

Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Little is known about the signaling mechanisms which function downstream of Robo to mediate repulsion. Here, we present genetic and biochemical evidence that the Abelson (Abl) tyrosine kinase and its substrate Enabled (Ena) play direct and opposing roles in Robo signal transduction. Genetic interactions support a model in which Abl functions to antagonize Robo signaling, while Ena is required in part for Robo's repulsive output. Both Abl and Ena can directly bind to Robo's cytoplasmic domain. A mutant form of Robo that interferes with Ena binding is partially impaired in Robo function, while a mutation in a conserved cytoplasmic tyrosine that can be phosphorylated by Abl generates a hyperactive Robo receptor.

PubMed Disclaimer

Similar articles

• Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.
  Fan X, Labrador JP, Hing H, Bashaw GJ. Fan X, et al. Neuron. 2003 Sep 25;40(1):113-27. doi: 10.1016/s0896-6273(03)00591-9. Neuron. 2003. PMID: 14527437
• Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.
  Chance RK, Bashaw GJ. Chance RK, et al. PLoS Genet. 2015 Sep 3;11(9):e1005402. doi: 10.1371/journal.pgen.1005402. eCollection 2015 Sep. PLoS Genet. 2015. PMID: 26335920 Free PMC article.
• Chimeric axon guidance receptors: the cytoplasmic domains of slit and netrin receptors specify attraction versus repulsion.
  Bashaw GJ, Goodman CS. Bashaw GJ, et al. Cell. 1999 Jun 25;97(7):917-26. doi: 10.1016/s0092-8674(00)80803-x. Cell. 1999. PMID: 10399919
• Downstream of guidance receptors: entering the baroque period of axon guidance signaling.
  Schmucker D. Schmucker D. Neuron. 2003 Sep 25;40(1):4-6. doi: 10.1016/s0896-6273(03)00603-2. Neuron. 2003. PMID: 14527427 Review.
• Slit-Robo signaling.
  Blockus H, Chédotal A. Blockus H, et al. Development. 2016 Sep 1;143(17):3037-44. doi: 10.1242/dev.132829. Development. 2016. PMID: 27578174 Review.

Cited by

• The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche.
  Srinivasan S, Mahowald AP, Fuller MT. Srinivasan S, et al. Development. 2012 Apr;139(8):1381-90. doi: 10.1242/dev.070052. Epub 2012 Feb 29. Development. 2012. PMID: 22378638 Free PMC article.
• The Drosophila immunoglobulin gene turtle encodes guidance molecules involved in axon pathfinding.
  Al-Anzi B, Wyman RJ. Al-Anzi B, et al. Neural Dev. 2009 Aug 17;4:31. doi: 10.1186/1749-8104-4-31. Neural Dev. 2009. PMID: 19686588 Free PMC article.
• Mena and vasodilator-stimulated phosphoprotein are required for multiple actin-dependent processes that shape the vertebrate nervous system.
  Menzies AS, Aszodi A, Williams SE, Pfeifer A, Wehman AM, Goh KL, Mason CA, Fassler R, Gertler FB. Menzies AS, et al. J Neurosci. 2004 Sep 15;24(37):8029-38. doi: 10.1523/JNEUROSCI.1057-04.2004. J Neurosci. 2004. PMID: 15371503 Free PMC article.
• A WASp-VASP complex regulates actin polymerization at the plasma membrane.
  Castellano F, Le Clainche C, Patin D, Carlier MF, Chavrier P. Castellano F, et al. EMBO J. 2001 Oct 15;20(20):5603-14. doi: 10.1093/emboj/20.20.5603. EMBO J. 2001. PMID: 11598004 Free PMC article.
• Abelson kinase regulates epithelial morphogenesis in Drosophila.
  Grevengoed EE, Loureiro JJ, Jesse TL, Peifer M. Grevengoed EE, et al. J Cell Biol. 2001 Dec 24;155(7):1185-98. doi: 10.1083/jcb.200105102. Epub 2001 Dec 24. J Cell Biol. 2001. PMID: 11756472 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • BioCyc
  • FlyBase
  • Gene Ontology
  • GlyGen glycoinformatics resource
  • PhosphoSitePlus

• Miscellaneous

  • NCI CPTAC Assay Portal
  • SciCrunch