The polymeric immunoglobulin receptor transports the polymeric immunoglobulins, IgA and IgM (pIg) into a wide variety of mucosal secretions, including bile. These antibodies form the first line of immunologic defense against infection, and their transport is deranged in several diseases. The pIg receptor (pIg-R) undergoes a variety of sorting steps in its transport across the cell. Many of these steps are mediated by proteins that interact with the cytoplasmic tail of the pIg-R. The goal of this research is to identify and characterize proteins from rat liver that bind to this cytoplasmic tail and mediate sorting. The cytoplasmic tail has been expressed as a recombinant protein fragment in E. coli, purified with a monoclonal antibody, and coupled to a solid matrix for affinity chromatography. In preliminary experiments cytosolic proteins from Madin-Darby canine kidney cells have been passed over this matrix, and several proteins that specifically bind to the tail of pIg-R have been identified. However, it is difficult to purify useful amounts of these proteins from these cultured cells. Rat liver expresses very large amounts of the pIg-R, and so cytosolic proteins from rat liver will be used in this pilot study as a source to purify useable quantities of these proteins. Moreover, well-characterized endosomal membrane fractions from rat liver may also contain other proteins that interact with the pIg-R cytoplasmic tail. Therefore, we will prepare non-denaturing detergent extracts of these membranes which will also be used as starting material for affinity chromatography. These proteins will be used for raising antibodies, which will be used for immunocytochemical localization. These antibodies will also be used to clone cDNA's for these proteins, which will be sequenced. Finally, the biochemical functions of these proteins will be studied in a variety of in vivo and in vitro assays.

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