MOLECULAR SIGNALS FOR TRAFFICKING SURFACTANT PROTEIN B

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DESCRIPTION (Adapted from the applicant's abstract): In this proposal, it is hypothesized that 1) movement of proSP-B, intermediates, and mature SP-B8 to the lamellar body is facilitated by organelle-specific compartmentalization of proSP-b processing, and 2) signals contained within the N- and C-terminal peptides flanking mature SP-B are important in trafficking SP-B to the lamellar body. Studies in Specific Aim 1 will clarify the steps in processing of human SP-B, and localize intermediates and cleavage products to subcellular organelles through the use of epitope-specific antibodies and organelle-specific markers, as well as pharmacologic agents that interfere with organelle transfer. In Aim 2, a tagged SP-B cDNA using the FLAG-sequence will be developed to track recombinant SP-B through type 2 cells on a background of endogenous SP-B production. Key regions of the N- and C-terminal peptides of proSP-B will be altered to examine aberrant trafficking of the recombinant SP-B protein. These studies will be carried out in human fetal lung explants which in culture develop a large stable population of type 2 cells suitable for studying processing and trafficking of SP-B.