Little is known of the molecular components that transduce mechanical stimuli in specialized sensory cells. The goal of this project is to investigate the function of the unc gene product in the mechanosensory cells of Drosophila. Disruption of this gene eliminates touch and hearing; in addition, unc mutant males have immotile sperm. The sensory defects in unc mutants occur in a class of ciliated cells that includes vertebrate photoreceptors and olfactory cells as well as many invertebrate sensory receptors. The combination of sensory and sperm defects suggests that unc is required for normal ciliary differentiation or operation. Defects in ciliary components are potentially involved in human conditions such as retinal degeneration, deafness, male sterility, or situs inversus. The unc gene has recently been cloned and while it includes domains found in cytoskeletal and axonemal motor proteins such as myosins and dyneins- a nucleotide-binding P-loop and a coiled-coil domain-it is not clearly related by sequence similarity to these or to any known proteins. It is proposed to: 1) Study the cellular and subcellular distribution of UNC during development. 2) Use electron microscopy to study the axonemal structure of unc mutant sperm. 3) Test if nucleotide binding is required for unc function, by altering conserved residues in the P-loop and coiled coil domain- it is not cellular and subcellular distribution of UNC during development. 2) Use electron microscopy to study the axonemal structure of unc mutant sperm. 3) Test if nucleotide binding is required for unc function, by altering conserved residues in the P-loop. 4) Search for proteins that interact with the UNC protein using the yeast two hybrid screen.
