The role of Cad99C, the Drosophila Usher Syndrome Protocadherin, in light-induced eye degeneration and apical membrane dynamics. Se-Yeon Chung, Deborah Andrew. Dept Cell Biol, Johns Hopkins Univ, Baltimore, MD.

   Usher Syndrome (USH) is the most frequent cause of hereditary deaf-blindness in humans. The gene products of ten USH disease genes have been identified so far, most of which are highly conserved from flies to humans. Cad99C, the Drosophila orthologue of human Usher cadherin PCDH15, is strongly expressed in embryonic tubular organs, including the salivary gland and trachea, where the apical membranes undergo dynamic changes during tube morphogenesis. Cad99C localizes to the apical domains suggesting a role in apical membrane dynamics. Our studies on Cad99C in the embryonic salivary gland revealed that Cad99C functions to regulate lumenal dimensions. Confocal and TEM analysis revealed that overexpression of Cad99C causes a dramatic increase in apical membrane at the expense of other cellular membrane domains. We also show that the intracellular domain of Cad99C is necessary for its apical targeting and that Cad99C mislocalization to the basolateral membrane results in a change in epithelial cell morphology from columnar to spherical, suggesting that Cad99C may promote cell-matrix interactions over cell-cell interactions. By learning how the USH genes function at the cellular and molecular level during the formation of relatively simple Drosophila tissues, we expect to gain additional key insight into how the USH genes function in human development and disease.