Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca(2+)-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 and vesicle 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 proteins. 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). The physiological role of PITP was previously unknown. We also find that SEC14p, the yeast phosphatidylinositol transfer protein which is essential for constitutive secretion, 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.
Hay
J C
JC
Program in Cell and Molecular Biology, University of Wisconsin, Madison 53706.
Martin
T F
TF
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells; D010716:Phosphatidylinositols / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins
D002352:Carrier Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D002118:Calcium; D009638:Norepinephrine