UNC-101, A GENE REQUIRED FOR MANY ASPECTS OF CAENORHABDITIS-ELEGANS DEVELOPMENT AND BEHAVIOR, ENCODES A CLATHRIN-ASSOCIATED PROTEIN

Our genetic analysis indicates that the unc-101 gene of Caenorhabditis elegans is required for many aspects of development and behavior, inc luding negative regulation of vulval differentiation. We have cloned u nc-101 and found that it encodes a homolog of the mammalian medium cha ins of clathrin-associated protein complexes located at the trans-Golg i and the plasma membrane, AP47 and AP50, respectively. Therefore, cla thrin-mediated events might contribute to the negative regulation of v ulval differentiation. Comparison of sequences, including a full-lengt h sequence of a C. elegans AP50 homolog, reveals that UNC-101 is most closely related to AP47. Mouse AP47 and nematode UNC-101 proteins are functionally equivalent as assayed in transgenic nematodes. We have se quenced the mutant alleles of unc-101 identified in various genetic sc reens and shown that all but one are deletions or nonsense mutations, suggesting that these alleles severely reduce unc-101 function.