UBC Theses and Dissertations
Functional roles of phospholipids in exocytosis Nayar, Rajiv
Cell secretion by exocytosis involves fusion between secretory granules and the surrounding plasma membrane, which results in the extracellular release of the granule contents. This event is triggered by the influx of Ca²⁺ on stimulation, which is accompanied by an increased conversion of the lipid phosphatidylinositol (PI) to diacylglycerol, to phosphatide acid (PA) and then back to PI. This work is concerned with the roles of phospholipids in exocytosis, both with regard to the Ca²⁺-stimulated fusion event itself and the roles of PI and intermediates in the PI cycle. Three topics are considered in detail, namely the physical properties of PI in pure and mixed lipid systems, the possible ability of PA to act as a Ca²⁺ ionophore and the influence of the plasma membrane inner monolayer lipid composition on the fusion event vital to the completion of exocytosis. It is shown by, employing ³¹P-NMR and freeze-fracture techniques, that PI adopts the bilayer organization in isolation and is particularly effective for stabilizing this organization when mixed with "non-bilayer" lipids both in the absence and presence of Ca²⁺. Alternatively, PA in large unilamellar vesicles exhibits properties consistent with Ca²⁺ ionophore capabilities. Finally, vesicles composed of phosphatidylethanolamine and phosphatidylserine (which possibly mimics the plasma membrane inner monolayer composition) can act as adjuncts to Ca²⁺-stimulated release of chromaffin granule contents. Theses results are consistent with the possibility that intermediates of the PI-response (e.g. PA) can enhance Ca²⁺ influx, and indicate that the plasma membrane inner monolayer lipid composition of the secretory cell may play a vital role in the secretory event.
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