Molecular composition of intercellular junctions in the organ of Corti. The complex chain of events involved in sensory transduction can be appreciated only by taking into account inter-cellular interactions within the organ of Corti, a structure whose emergent frequency-filtering properties depend primarily on how it behaves mechanically. Therefore a very important issue is that of force transmission at the junction between hair cells and supporting cells. We are studying the structure and molecular composition of the highly developed tight junction which interlocks hair cells and supporting cells in the reticular lamina of the organ of Corti. This junction alone, in the absence of an adherens junction, creates a reinforced structure that can withstand the vigorous motion that occurs during sound transduction. We showed that it contains ZO-1 and at least one of the adherens junction components, b-catenin, which suggests that the OHC tight junction is an enhanced hybrid tight-adherens junction. This unique junction has a dual function as a permeability barrier and adhesion complex and may derive at least part of its adhesive capacity from molecular components of the adherens junction. We will continue our studies of these junctions using improved imaging and immunocytochemistry techniques. In addition we plan to initiate a project in collaboration with Dr. Robert Wenthold, NIDCD, to investigate novel proteins involved in the formation of hair cell-supporting cell junctions. We will be using a guinea pig organ of Corti library for yeast two-hybrid screening which has been established and tested in Dr. Wenthold's laboratory. As bait we will use known junctional proteins such as occludin and ZO-1 to identify interacting proteins expressed in hair cells and supporting cells.