A highly dynamic ER-derived phosphatidylinositol synthesizing organelle supplies phosphoinositides to cellular membranes

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NICHD	CELLBIO-7

Authors

• YJ Kim
• T Balla

Abstract

Phosphoinositides (PIs) are lipid signaling molecules with critical roles in membrane biogenesis, vesicular trafficking and signaling. PIs are phosphorylation products of phosphatidylinositol (PtdIns) but the localization and mechanism of PtdIns distribution between membranes are poorly understood. Here we describe a hitherto unrecognized highly mobile membrane compartment that is the site of PtdIns synthesis and the source of all PIs. We show that the PtdIns synthesizing enzyme, PIS is associated with a rapidly moving compartment that originates from the ER and which makes ample contact with various organelles, including the plasma membranes. In contrast, the CDP-diacylglycerol synthase (CDS) enzymes that provide PIS with its lipid substrate are found exclusively in the tubular ER. We also demonstrate that expression of a PtdIns-specific bacterial phospholipase C generates diacylglycerol in rapidly moving cytoplasmic objects confirming the presence of PtdIns primarily in the newly recognized cytoplasmic structures. We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to other membranes during multiple contacts by yet to be defined lipid transfer mechanisms.

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