This research project is focused on determining the structure and function relationship of the gap junction channel and the contribution of gap junctional communication to the processes of embryonic development and differentiation. The specific objectives for this study include the following. 1. The structure and function relationship of the rat liver gap junction channels and a baculovirus-derived gap junction channel will be determined by initially isolating channel oligomers from these two sources. The oligomers will then be used for the following: (1) a characterization of their structural and biochemical properties; (2) efforts to crystallize the isolated oligomers for analysis by electron microscopy and potentially X- ray diffraction; (3) reconstitution of the oligomers into black membrane systems where the channel conductance properties of the reconstituted can be characterized biophysically; (4) to determine if the isolated oligomers contain a single gene product (homo-oligomer) or multiple gene products (hetero-oligomer); and finally (5) to determine the contribution of the sequences in the extracellular domains. 2. Gap junctional communication will be studied in a number of systems that include: Xenopus embryogenesis, mouse embryogenesis and organogenesis, implantation and parturition in the rat, and muscle differentiation using a mouse cell culture system. IN addition the contribution of gap junctional communication to some of these processes will be analyzed by modifying communication with various perturbation approaches.
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