FUNCTIONAL ORGANIZATION OF MEMBRANE DOMAINS IN THE LENS

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Lens fiber cells are the longest epithelial cells in the body. Despite their length, fiber cells maintain a polarized distribution of membrane proteins in discrete basal, lateral and apical membrane domains. The unique composition of these domains is established early in development and actively maintained, even during the rapid cellular elongation that accompanies fiber cell differentiation. This proposal utilizes an integrated approach to study membrane dynamics in the living lens. Initial studies will focus on the control of membrane synthesis in various regions of the lens and mechanisms underlying intracellular transport of membrane vesicles. A simple, one-step, technique for purifying components of the basal membrane domain has been developed. Using this method, components of the basal membrane domain will be identified. The arrangement of membrane and cytoskeletal elements at the basal membrane domain suggests a novel role in accommodation and/or migration. Experiments will test the role of the basal membrane domain in these functions. A striking feature of the lateral membranes in the lens is the presence of an extraordinary abundance of gap junctions. Experiments are proposed that examine the formation and stability of lens gap junction plaques. In addition a novel diffusion pathway has been identified in central fiber cells and this pathway will be characterized. Tyrosine phosphorylation of lateral membrane substrates occurs when fiber cells reach the sutures. The phosphorylated proteins will be identified and the developmental cues that trigger membrane phosphorylation will be determined. These studies will provide important data on membrane dynamics in the lens. These studies are particularly timely because lens membrane defects (both genetic and biochemical) have recently been shown to underlie many types of cataract in humans.