C. elegans VAB-8 and UNC-73 regulate the SAX-3 receptor to direct cell and growth-cone migrations

Nat Neurosci. 2007 Feb;10(2):169-76. doi: 10.1038/nn1834. Epub 2007 Jan 21.

Abstract

During nervous system development, a small number of conserved guidance cues and receptors regulate many axon trajectories. How could a limited number of cues and receptors regulate such complex projection patterns? One way is to modulate receptor function. Here we show that the Caenorhabditis elegans kinesin-related protein VAB-8L, which is necessary and sufficient for posterior cell and growth-cone migrations, directs these migrations by regulating the levels of the guidance receptor SAX-3 (also known as robo). Genetic experiments indicate that VAB-8L and the Rac guanine nucleotide exchange factor activity of UNC-73 (trio) increase the ability of the SLT-1 (slit) and UNC-6 (netrin) guidance pathways to promote posterior guidance. The observations of higher SAX-3 receptor abundance in animals with increasing amounts of VAB-8L, and of physical interactions between UNC-73 and both VAB-8L and the intracellular domain of the SAX-3, support a model whereby VAB-8L directs cell and growth-cone migrations by promoting localization of guidance receptors to the cell surface.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Differentiation / physiology
  • Cell Movement / physiology*
  • Cues
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nervous System / cytology
  • Nervous System / embryology*
  • Nervous System / metabolism
  • Netrins
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Nerve Tissue Proteins
  • Netrins
  • Receptors, Immunologic
  • UNC-6 protein, C elegans
  • UNC-73 protein, C elegans
  • roundabout protein
  • slt-1 protein, C elegans
  • vab-8 protein, C elegans
  • rac GTP-Binding Proteins