UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans

R Steven; T J Kubiseski; H Zheng; S Kulkarni; J Mancillas; A Ruiz Morales; C W Hogue; T Pawson; J Culotti

doi:10.1016/s0092-8674(00)81406-3

UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans

Cell. 1998 Mar 20;92(6):785-95. doi: 10.1016/s0092-8674(00)81406-3.

Authors

R Steven¹, T J Kubiseski, H Zheng, S Kulkarni, J Mancillas, A Ruiz Morales, C W Hogue, T Pawson, J Culotti

Affiliation

¹ Samuel Lunenfeld Research Institute of Mt. Sinai Hospital, Toronto, Ontario, Canada.

PMID: 9529254
DOI: 10.1016/s0092-8674(00)81406-3

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Axons / chemistry
Axons / physiology
Blood Proteins / genetics
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / genetics
Caenorhabditis elegans Proteins*
Cell Division / physiology
GTP Phosphohydrolases / metabolism
GTPase-Activating Proteins
Gene Expression Regulation, Developmental
Genes, Reporter
Helminth Proteins / genetics*
Helminth Proteins / metabolism
Molecular Sequence Data
Motor Neurons / physiology
Motor Neurons / ultrastructure
Mutagenesis, Insertional
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Neurites / chemistry
Neurites / physiology*
Phenotype
Phosphoproteins*
Proteins / metabolism*
Recombinant Fusion Proteins / genetics
Sequence Homology, Amino Acid

Substances

Blood Proteins
Caenorhabditis elegans Proteins
GTPase-Activating Proteins
Helminth Proteins
Nerve Tissue Proteins
Phosphoproteins
Proteins
Recombinant Fusion Proteins
UNC-73 protein, C elegans
platelet protein P47
GTP Phosphohydrolases

Associated data

GENBANK/AF048834
GENBANK/AF048835