Article abstract
Nature Neuroscience 10, 169 - 176 (2007)
Published online: 21 January 2007 | doi:10.1038/nn1834
C. elegans VAB-8 and UNC-73 regulate the SAX-3 receptor to direct cell and growth-cone migrations
Natsuko Watari-Goshima1, Ken-ichi Ogura2, Fred W Wolf1,4, Yoshio Goshima2,3 & Gian Garriga1
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.
- Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720-3204, USA.
- Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
- CREST Japan Science and Technology Corporation Kawaguchi 332-0012, Japan.
- Current address: Ernest Gallo Clinic & Research Center, 5858 Horton St., Suite 200, Emeryville, California 94608, USA.
Correspondence to: Gian Garriga1 e-mail: garriga@berkeley.edu
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