UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans.
unc-73 is required for cell migrations and axon guidance in C. elegans and encodes overlapping isoforms of 283 and 189 kDa that are closely related to the vertebrate Trio and Kalirin proteins, respectively. UNC-73A contains, in order, eight spectrin-like repeats, a Dbl/Pleckstrin homology (DH/PH) element, an SH3-like domain, a second DH/PH element, an immunoglobulin domain, and a fibronectin type III domain. UNC-73B terminates just downstream of the SH3-like domain. The first DH/PH element specifically activates the Rac GTPase in vitro and stimulates actin polymerization when expressed in Rat2 cells. Both functions are eliminated by introducing the S1216F mutation of unc-73(rh40) into this DH domain. Our results suggest that UNC-73 acts cell autonomously in a protein complex to regulate actin dynamics during cell and growth cone migrations.
Steven
R
R
Samuel Lunenfeld Research Institute of Mt. Sinai Hospital, Toronto, Ontario, Canada.
Kubiseski
T J
TJ
Zheng
H
H
Kulkarni
S
S
Mancillas
J
J
Ruiz Morales
A
A
Hogue
C W
CW
Pawson
T
T
Culotti
J
J
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology; D001798:Blood Proteins / Q000235:genetics; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016501:Neurites / Q000737:chemistry / Q000502:physiology*; D010641:Phenotype; D010750:Phosphoproteins; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D001798:Blood Proteins; D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C111263:UNC-73 protein, C elegans; C039077:platelet protein P47; D020558:GTP Phosphohydrolases