Hay J C, Martin T F
Program in Cell and Molecular Biology, University of Wisconsin, Madison 53706.
Nature. 1993 Dec 9;366(6455):572-5. doi: 10.1038/366572a0.
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.
通过鉴定具有已知生化活性的参与蛋白，有助于阐明分泌细胞中分泌颗粒与质膜的钙调节融合所涉及的反应。对可能在钙调节分泌中起作用的胞质和囊泡蛋白的成功表征，尚未揭示这一过程背后的分子事件。调节性分泌由依次发生的引发和触发步骤组成，这两个步骤分别依赖于ATP和Ca2+，并需要不同的胞质蛋白。对引发特异性因子（PEP蛋白）的表征应能鉴定出需要ATP的反应。在这里，我们表明哺乳动物引发因子之一（PEP3）与磷脂酰肌醇转移蛋白（PITP）相同。PITP的生理作用以前未知。我们还发现，酵母磷脂酰肌醇转移蛋白SEC14p对组成型分泌至关重要，它可以在引发过程中替代PEP3/PITP。我们的结果表明，磷脂转移蛋白在组成型和调节性分泌途径中的作用是保守的。
