Lipid Dynamics in the Golgi Apparatus

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The organelle membrane system of the eukaryotic cell is constituted by two complementary lipid `territories'. One originates from the endoplasmic reticulum (ER), where lipid and protein synthesis occurs, and the other is encompasses the trans-Golgi network (TGN), plasma membrane, and organelles of endo-lysosomal system. The lipid composition of TGN membrane is modified from that of earlier Golgi compartments by lipid transfer proteins that deliver lipids directly to TGN membrane at the endoplasmic reticulum (ER)-Golgi membrane contact site, and from local sphingolipid synthesis, principally sphingomyelin. Hence the composition of the TGN is refined to approximate that of the plasma membrane (PM); it is enriched in sphingolipid, cholesterol, and acidic phospholipids, while the ER/Golgi territory is relatively deficient of these lipid classes, even though most are produced there. Membrane of the TGN/PM territory is asymmetric, with sphingolipids restricted to the exofacial leaflet and acidic glycerophospholipids (chiefly PS and phosphoinositides) restricted to cytoplasmic membrane leaflets. There are expansive gaps of knowledge regarding the mechanisms that coordinate the synthesis and distribution of lipids and proteins between the two lipid territories of the cell. This research will address these gaps of knowledge, focusing on the trans and TGN Golgi compartments of the Golgi. We will investigate the roles and regulation of lipid transfer proteins that modify the membrane lipid composition of these compartments. Preliminary unpublished data identified a cohort of integral membrane signaling proteins that reside in the TGN and are intimately associated with sphingolipid. We will determine if any of these proteins function as sensors of Golgi lipid homeostasis, and we will test a hypotheses that they regulate release of distinct cohorts of secretory cargo into the TGN/PM lipid territory. This research promises to elucidate new information regarding the regulation of secretion by eukaryotic cells.