FUNCTIONAL-PROPERTIES OF THE UNC-64 GENE ENCODING A CAENORHABDITIS-ELEGANS SYNTAXIN

Phenotypes of Caenorhabditis elegans unc-18 and unc-64 gene mutations are similar. While unc-18 is known to be essential for normal synaptic transmission (Hosono, R., Hekimi, S., Kamiya, Y., Sassa, T., Murakami , S., Nishiwaki, S., Miwa, J., Taketo, A, and Kodaira, K.-I. (1992) J. Neurochem. 58, 1517-1525), the function of unc-64 remains unclear. He re we describe the cloning, and the molecular and genetic characteriza tion of the unc-64 gene, especially in relation to unc-18. unc-64 enco des a protein (C. elegans syntaxin) showing sequence and structural si milarities to mammalian syntaxin 1A. From unc-64, at least three types of poly(A)(+) RNA are transcribed, which encode two types of syntaxin that differ in the deduced transmembrane domain. In gene expression, unc-64 closely resembles unc-18, that is, both are expressed in neural cells, especially in motor neurons and neurons constituting head gang lions. C. elegans syntaxin binds to UNC-18 with high affinity. The unc -64 (e246) mutation producing a mild phenotype causes an Ala --> Val c onversion in the conserved COOH-terminal region in mammalian syntaxin 1A or Drosophila syntaxin-1A whose site is included in three types of transcripts. The binding of the mutant C. elegans syntaxin tb UNC-18 i s greatly reduced, indicating the mutation Site contributes to the bin ding.