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

Natsuko Watari-Goshima1, Ken-ichi Ogura, Fred W Wolf

  • 1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720-3204, USA.

Nature Neuroscience
|January 24, 2007
PubMed

Insights

The kinesin-related protein VAB-8L regulates cell migration during nervous system development by controlling the levels of the SAX-3 guidance receptor. This mechanism enhances posterior guidance pathways, ensuring proper axon trajectory formation.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Nervous system development relies on conserved guidance cues and receptors for complex axon trajectories.
  • The precise mechanisms by which limited molecular components orchestrate intricate projection patterns remain an area of active investigation.
  • Modulating receptor function is a proposed strategy for expanding the regulatory capacity of guidance systems.

Purpose of the Study:

  • To investigate the role of the Caenorhabditis elegans kinesin-related protein VAB-8L in directing cell and growth-cone migrations.
  • To elucidate how VAB-8L regulates the function of the guidance receptor SAX-3 (robo).
  • To understand the molecular interactions underlying VAB-8L-mediated guidance.

Main Methods:

  • Genetic manipulation in Caenorhabditis elegans to assess the necessity and sufficiency of VAB-8L.
  • Analysis of SAX-3 receptor abundance in response to varying VAB-8L levels.
  • Biochemical assays to detect physical interactions between UNC-73 (trio), VAB-8L, and the SAX-3 intracellular domain.

Main Results:

  • VAB-8L is necessary and sufficient for posterior cell and growth-cone migrations.
  • VAB-8L and UNC-73 (trio) activity enhance SLT-1 (slit) and UNC-6 (netrin) posterior guidance.
  • Increased VAB-8L levels correlate with higher SAX-3 receptor abundance on the cell surface.
  • Physical interactions confirmed between UNC-73, VAB-8L, and the SAX-3 intracellular domain.

Conclusions:

  • VAB-8L directs cell and growth-cone migrations by modulating SAX-3 receptor levels.
  • The VAB-8L-UNC-73 complex promotes SAX-3 localization to the cell surface, enhancing guidance.
  • This study reveals a novel mechanism for regulating guidance receptor availability to control complex neural wiring patterns.

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