ChBE Seminar Series: William Prinz
Tuesday, November 17, 2009
11:00 a.m.-12:15 p.m.
Room 2110 Chemical and Nuclear Eng. Bldg.
Professor J. Klauda
Moving Sterols and Signals Between Organelles at Membrane Contact Sites
Presented by William Prinz
National Institutes of Health (NIH)
The exchange of small molecules and signals between organelles is thought to occur at regions of membrane apposition called membrane contact sites (MSCs). However, few components of MCSs have been identified and little is known about how they function. The oxysterol-binding protein (OSBP)-related proteins (ORPs) are a large family of conserved lipid-binding proteins implicated in intracellular signaling, vesicular trafficking, and nonvesicular sterol transport. We have found that the ORPs in S. cerevisiae facilitate membrane contact and sterol transfer between bilayers at MCSs by a novel mechanism. The core lipid-binding domain present in all ORPs has two membrane-binding faces, allowing them to bind two membranes simultaneously. Remarkably, ORPs can transfer sterols between two membranes even while tightly bound to both, suggesting that ORPs can transport lipids without dissociating from membranes. The two membrane binding faces work cooperatively to transport lipid; ORP binding to phosphoinositides in one membrane greatly enhances the extraction and transfer of sterols from a second. Consistent with a role for ORPs at MCSs, we show that most of the seven ORPs in yeast are enriched at these regions, particularly between the endoplasmic reticulum and plasma membrane. Our findings define specific components of MCSs that simultaneously interact with each organelle, allowing them to sense and regulate the lipid content of both membranes.