PHOSPHATIDYLINOSITOL TRANSFER PROTEIN REQUIRED FOR ATP-DEPENDENT PRIMING OF CA2-ACTIVATED SECRETION()

ELUCIDATION of the reactions responsible for the calcium-regulated fus ion of secretory granules with the plasma membrane in secretory cells would be facilitated by the identification of participant proteins hav ing known biochemical activities. The successful characterization of c ytosolic1-3 and vesicle 4,5 proteins that may function in calcium-regu lated secretion has not yet revealed the molecular events underlying t his process. Regulated secretion consists of sequential priming and tr iggering steps which depend on ATP and Ca2+, respectively, and require distinct cytosolic proteins6. Characterization of priming-specific fa ctors (PEP proteins) should enable the ATP-requiring reactions to be i dentified. Here we show that one of the mammalian priming factors (PEP 3) is identical to phosphatidylinositol transfer protein (PITP)7. The physiological role of PITP was previously unknown. We also find that S EC14p, the yeast phosphatidylinositol transfer protein which is essent ial for constitutive secretion8-10, can substitute for PEP3/PITP in pr iming. Our results indicate that a role for phospholipid transfer prot eins is conserved in the constitutive and regulated secretory pathways .