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, including negative regulation of vulval differentiation. We have cloned unc-101 and found that it encodes a homolog of the mammalian medium chains of clathrin-associated protein complexes located at the trans-Golgi and the plasma membrane, AP47 and AP50, respectively. Therefore, clathrin-mediated events might contribute to the negative regulation of vulval differentiation. Comparison of sequences, including a full-length 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 sequenced the mutant alleles of unc-101 identified in various genetic screens and shown that all but one are deletions or nonsense mutations, suggesting that these alleles severely reduce unc-101 function.