title: The C. elegans UNC-23 protein, a member of the BCL-2-associated athanogene (BAG) family of chaperone regulators, interacts with HSP-1 to regulate cell attachment and maintain hypodermal integrity.
abstract: Mutations in the unc-23 gene in the free-living nematode, Caenorhabditis elegans result in detachment and dystrophy of the anterior body wall musculature and a bent-head phenotype when grown on solid substrate. We have determined that the unc-23 gene product is the nematode ortholog of the human BAG-2 protein, a member of the Bcl-2 associated athanogene (BAG) family of molecular chaperone regulators. We show that a functional GFP-tagged UNC-23 protein is expressed throughout development in several tissues of the animal, including body wall muscle and hypodermis, and associates with adhesion complexes and attachment structures within these 2 tissues. In humans, the BAG protein family consists of 6 members that all contain a conserved 45 amino acid BAG domain near their C-termini. These proteins bind to and modulate the activity of the ATPase domain of the heat shock cognate protein 70, Hsc70. We have isolated missense mutations in the ATPase domain of the C. elegans heat shock 70 protein, HSP-1 that suppress the phenotype exhibited by unc-23(e25) mutant hermaphrodites and we show that UNC-23 and HSP-1 interact in a yeast-2-hybrid system. The interaction of UNC-23 with HSP-1 defines a role for HSP-1 function in the maintenance of muscle attachment during development.
authors.affiliation: Department of Zoology; University of British Columbia ; Vancouver, British Columbia, Canada.
authors.forename: Poupak
authors.initials: P
authors.lastname: Rahmani
authors.affiliation: Department of Zoology; University of British Columbia ; Vancouver, British Columbia, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rogalski
authors.affiliation: Department of Zoology; University of British Columbia ; Vancouver, British Columbia, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
keywords: BAG chaperones; Caenorhabditis elegans; UNC-23 protein; heat shock protein; muscular dystrophy; shear stress