Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca²⁺-activated secretion

Elucidation of the reactions responsible for the calcium-regulated fusion of secretory granules with the plasma membrane in secretory cells would be facilitated by the identification of participant proteins having known biochemical activities. The successful characterization of cytosolic^1-3 and vesicle⁴ proteins that may function in calcium-regulated secretion has not yet revealed the molecular events underlying this process. Regulated secretion consists of sequential priming and triggering steps which depend on ATP and Ca²⁺, respectively, and require distinct cytosolic proteins⁶. Characterization of priming-specific factors (PEP proteins) should enable the ATP-requiring reactions to be identified. Here we show that one of the mammalian priming factors (PEP3) is identical to phosphatidylinositol transfer protein (PITP)⁷. The physiological role of PITP was previously unknown. We also find that SEC14p, the yeast phosphatidylinositol transfer protein which is essential for constitutive secretion^8-10, can substitute for PEP3/PITP in priming. Our results indicate that a role for phospholipid transfer proteins is conserved in the constitutive and regulated secretory pathways.