ABSTRACT
The past 20 years have witnessed tremendous progress in our understanding of the molecular machinery that controls protein and membrane transport between organelles (Scheckman R, Orci L. Coat proteins and vesicle budding. Science 1996;271: 1526-1533 and Rothman JE. Mechanisms of intracellular protein transport. Nature 1994;372: 55-63.) The research efforts responsible for these impressive advances have largely focused on the identification and characterization of protein factors that participate in membrane trafficking events. The role of membranes and their lipid constituents has received considerably less attention. Indeed, until rather recently, popular models for mechanisms of membrane trafficking had relegated membrane lipids to the status of a passive platform, subject to deformation by the action of coat proteins whose polymerization and depolymerization govern vesicle budding and fusion reactions. The 1990s, and particularly its last half, has brought fundamental reappraisals of the interface of lipids and lipid metabolism in regulating intracellular membrane trafficking events. Some of the emerging themes are reviewed here.
Subject(s)
Biological Transport/physiology , Membrane Lipids/metabolism , Saccharomyces cerevisiae Proteins , 1-Phosphatidylinositol 4-Kinase/metabolism , Animals , Carrier Proteins/physiology , Clathrin-Coated Vesicles/metabolism , Endocytosis , Exocytosis , Fungal Proteins/metabolism , Humans , Lipid Bilayers , Mammals/metabolism , Membrane Proteins/metabolism , Mice , Mice, Knockout , Models, Biological , Phosphatidylcholines/metabolism , Phosphatidylinositol Diacylglycerol-Lyase , Phosphatidylinositols/metabolism , Phospholipid Transfer Proteins , Phosphoric Monoester Hydrolases/metabolism , Protein Transport/physiology , Saccharomyces cerevisiae/metabolism , Type C Phospholipases/metabolismABSTRACT
Yeast phosphatidylinositol transfer protein (Sec14p) is essential for Golgi secretory function. It is widely accepted, though unproven, that phosphatidylinositol transfer between membranes represents the physiological activity of phosphatidylinositol transfer proteins (PITPs). We report that Sec14pK66,239A is inactivated for phosphatidylinositol, but not phosphatidylcholine (PC), transfer activity. As expected, Sec14pK66,239A fails to meet established criteria for a PITP in vitro and fails to stimulate phosphoinositide production in vivo. However, its expression efficiently rescues the lethality and Golgi secretory defects associated with sec14-1ts and sec14 null mutations. This complementation requires neither phospholipase D activation nor the involvement of a novel class of minor yeast PITPs. These findings indicate that PI binding/transfer is remarkably dispensable for Sec14p function in vivo.
