VAB-8, UNC-73 and MIG-2 regulate axon polarity and cell migration functions of UNC-40 in C. elegans

Nat Neurosci. 2007 Feb;10(2):161-8. doi: 10.1038/nn1835. Epub 2007 Jan 21.

Abstract

One of the most intriguing features of axons is their ability to pioneer precise paths to their targets. How guidance-cue information is interpreted and integrated to form intricate neuronal networks has not been fully deciphered. Using Caenorhabditis elegans, we show that highly conserved receptors that guide pioneer axons along the dorsoventral axis, such as UNC-40 and SAX-3 (receptors for UNC-6 and SLT-1 guidance cues, respectively), can be co-opted to affect axon and cell migrations along the anterior-posterior axis. We further identify the kinesin-related VAB-8 protein as an upstream regulator of UNC-40, illuminating VAB-8's mechanism of action in determining the polarity of cell and axon migration. Finally, we show that UNC-73 and its target MIG-2 function with VAB-8 as upstream regulators of UNC-40 and that MIG-2 activity specifies UNC-40 subcellular localization. These data are indicative of previously unidentified regulatory roles for VAB-8 and small GTPases, which act together to regulate guidance receptor functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / ultrastructure
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Differentiation / physiology
  • Cell Movement / physiology*
  • Cell Polarity / physiology
  • Cues
  • Gene Expression Regulation, Developmental / physiology
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism
  • Nerve Growth Factors / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nervous System / cytology
  • Nervous System / embryology
  • Nervous System / metabolism
  • Netrins
  • Neural Pathways / cytology
  • Neural Pathways / embryology
  • Neural Pathways / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Nerve Growth Factor / metabolism
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Netrins
  • Receptors, Immunologic
  • Receptors, Nerve Growth Factor
  • UNC-40 protein, C elegans
  • UNC-6 protein, C elegans
  • UNC-73 protein, C elegans
  • roundabout protein
  • vab-8 protein, C elegans
  • Mig-2 protein, C elegans
  • Monomeric GTP-Binding Proteins
  • rac GTP-Binding Proteins