The DH-PH Region of the Giant Protein UNC-89 Activates RHO-1 GTPase in Caenorhabditis elegans Body Wall Muscle

Hiroshi Qadota, Anne Blangy, Ge Xiong, Guy M. Benian

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)747-752
Number of pages6
JournalJournal of Molecular Biology
Volume383
Issue number4
DOIs
StatePublished - Nov 21 2008
Externally publishedYes

Keywords

  • C. elegans
  • GEF
  • muscle
  • rho
  • UNC-89

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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