Lipid Dynamics in the Golgi Apparatus

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 Preliminary unpublished data identified a cohort of integral membrane signaling proteins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.

Grant Number: 5R35GM144096-04
NIH Institute/Center: NIH
Principal Investigator: Christopher Burd