VAB-8, UNC-73 and MIG-2 regulate axon polarity and cell migration functions of UNC-40 in C. elegans.
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.
Levy-Strumpf
Naomi
N
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Culotti
Joseph G
JG
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D003463:Cues; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000075385:Netrins; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D020559:Monomeric GTP-Binding Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011971:Receptors, Immunologic; D017475:Receptors, Nerve Growth Factor; D020744:rac GTP-Binding Proteins; D000097905:Roundabout Proteins; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C111263:UNC-73 protein, C elegans; C112201:vab-8 protein, C elegans; C442327:Mig-2 protein, C elegans