C. elegans VAB-8 and UNC-73 regulate the SAX-3 receptor to direct cell and growth-cone migrations.
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.
Watari-Goshima
Natsuko
N
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720-3204, USA.
Ogura
Ken-ichi
K
Wolf
Fred W
FW
Goshima
Yoshio
Y
Garriga
Gian
G
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003463:Cues; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000075385:Netrins; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011971:Receptors, Immunologic; D020744:rac GTP-Binding Proteins; D000097905:Roundabout Proteins; C078146:UNC-6 protein, C elegans; C111263:UNC-73 protein, C elegans; C492285:slt-1 protein, C elegans; C112201:vab-8 protein, C elegans