David Perlmutter

University of Pittsburgh School of Medicine; Pittsburgh PA, United States of America Washington University School of Medicine; Saint Louis MO, United States of America

lqIs193

Caenorhabditis elegans

[TIAM-1(DH(DEAD)PH)]

mig-2 : unc-73

"The UNC-73B DH domain activates CeRAC1 and MIG-2."

ced-10 : unc-73

"The UNC-73B DH domain activates CeRAC1 and MIG-2."

mig-2 : unc-89

"The UNC-89 DH-PH region interacts with RhoGTPases in vitro."

cdc-42 : unc-89

"The UNC-89 DH-PH region interacts with RhoGTPases in vitro."

ced-10 : unc-89

"The UNC-89 DH-PH region interacts with RhoGTPases in vitro."

rho-1 : unc-89

"The UNC-89 DH-PH region interacts with RhoGTPases in vitro."; "UNC-89 is an exchange factor for RHO-1."

rho-1 : unc-89

"The UNC-89 DH-PH region interacts with RhoGTPases in vitro."; "UNC-89 is an exchange factor for RHO-1."

Qadota H et al. (2008) J Mol Biol "The DH-PH region of the giant protein UNC-89 activates RHO-1 GTPase in Caenorhabditis elegans body wall muscle."

Xiong G, Qadota H, Blangy A, Benian GM

[J Mol Biol, 2008]

Mutation of the Caenorhabditis elegans gene unc-89 results in disorganization of muscle A-bands. unc-89 encodes a giant polypeptide (900 kDa) containing a DH domain followed by a PH domain at its N terminus, which is characteristic of guanine nucleotide exchange factor proteins for Rho GTPases. To obtain evidence that the DH-PH region has activity toward specific Rho family small GTPases, we conducted an experiment using the yeast three-hybrid system. The DH-PH region of UNC-89 has exchange activity for RHO-1 (C. elegans RhoA), but not for CED-10 (C. elegans Rac), MIG-2 (C. elegans RhoG), or CDC-42 (C. elegans Cdc42). The DH domain alone has similar activity for RHO-1. An in vitro binding assay demonstrates interaction between the DH-PH region of UNC-89 and each of the C. elegans Rho GTPases. Partial knockdown of rho-1 in C. elegans adults showed a pattern of disorganization of myosin thick filaments similar to the phenotype caused by unc-89 (su75), a mutant allele in which all of the isoforms containing the DH-PH region are missing. Taken together, we propose a model in which the DH-PH region of UNC-89 activates RHO-1 GTPase for organization of myosin filaments in C. elegans muscle cells.