THE TRA-3 SEX DETERMINATION GENE OF CAENORHABDITIS-ELEGANS ENCODES A MEMBER OF THE CALPAIN REGULATORY PROTEASE FAMILY

The Caenorhabditis elegans sex determination gene tra-3 is required fo r the correct sexual development of the soma and germ line in hermaphr odites, while being fully dispensable in males. Genetic analysis of tr a3 has suggested that its product may act as a potentiator of another sex determination gene, tra-2. Molecular analysis reported here reveal s that the predicted tra-3 gene product is a member of the calpain fam ily of calcium-regulated cytosolic proteases, though it lacks the calc ium binding regulatory domain. Calpains are regulatory processing prot eases, exhibiting marked substrate specificity, and mutations in the p 94 isoform underlie the human hereditary condition limb-girdle muscula r dystrophy type 2A. The molecular identity of TRA-3 is consistent wit h previous genetic analysis which suggested that tra3 plays a very sel ective modulatory role and is required in very small amounts. Based on these observations and new genetic data, we suggest a refinement of t he position of tra-3 within the sex determination cascade and discuss possible mechanisms of action for the TRA-3 protein.