The intent of this project is to extend previous work by the applicant on the actin system of PMN and related cells to the interface between the PMN actin system and the PMN plasma membrane on the premise that this interaction is central to mechanisms of PM locomotion, phagocytosis, and exocytosis, the PMN functions responsible for host defense against pyogenic infection and for the pathogenesis of inflammation. One specific goal is to identify and characterize a putative PMN transmembrane-glycoprotein linked to the actin system through the molecule actin-binding protein (ABP) using immunochemical and molecular genetic techniques. The existence of this glycoprotein is inferred from preliminary studies involving platelets and kidney tubule cells and the theoretical consideration that such molecules must exist to provide membrane stabilization and traction for intracellular contractile events. The second major goal is to examine what are proposed as less stable membrane/actin associations involved in the metabolically controlled propulsion of PMN membranes accompanying pseudopod protrusions in locomotion and phagocytosis. This project capitalizes upon recent evidence for membrane phospholipid regulation of the actin filament length-modulating protein, gelsolin and will involve biochemical and morphological studies of gelsolin/membrane lipid interactions in PMN. In addition, collaborative studies with other projects will examine effects of membrane lipid modification on these interactions and, conversely, the effects of these interactions on a PMN membrane signalling system. A third project will ultrastructurally examine membrane stability in different domains of PM during locomotion.
Showing the most recent 10 out of 98 publications
