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ATP-dependent inositide phosphorylation required for Ca2+-activated secretion

Nature volume 374, pages 173–177 (1995)Cite this article

Abstract

REGULATED fusion of secretory granules with the plasma membrane in secretory cells requires ATP, Ca2+ and cytosolic1-3 as well as membrane4 proteins. ATP-dependent steps in Ca2+-activated secretion from PC 12 cells require three cytosolic PEP proteins (priming in exocytosis proteins, PEP1–3)5,6, the identity of which will provide insights into the required ATP-using reactions. PEP3 was recently identified as phosphatidylinositol transfer protein (PtdlnsTP)6, and here we report that PEP1 consists of the type I phosphatidylinositol-4-phosphate 5-kinase (PtdlnsPSK). The roles of PEP3/PtdInsTP and PEP1/ PtdlnsPSK in sequential phosphoinositide recruitment and phosphorylation explains their synergistic activity in ATP-dependent priming. Moreover, inhibition of Ca2+-activated secretion by PtdIns(4,5)P2-specific antibodies and phospholipase C implies that 5-phosphorylated inositides play a novel, necessary role in the regulated secretory pathway. The results indicate that lipid kinase-mediated phosphorylation is an important basis for ATP use in the exocytotic pathway.

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Author notes

  1. Jesse C. Hay

    Present address: Depart of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford, California, 94305, USA

Authors and Affiliations

  1. Program in Cell and Molecular Biology, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Jesse C. Hay & Phillip L Fisette

  2. Department of Pharmacology, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Glenn H Jenkins & Richard A. Anderson

  3. Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Thomas F. J. Martin

  4. Department of Molecular Oncology, The University of Tokyo, Tokyo, 108, Japan

    Kiyoko Fukami & Tadaomi Takenawa

Authors
  1. Jesse C. Hay
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  2. Phillip L Fisette
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  3. Glenn H Jenkins
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  4. Kiyoko Fukami
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  5. Tadaomi Takenawa
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  6. Richard A. Anderson
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  7. Thomas F. J. Martin
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Hay, J., Fisette, P., Jenkins, G. et al. ATP-dependent inositide phosphorylation required for Ca2+-activated secretion. Nature 374, 173–177 (1995). https://doi.org/10.1038/374173a0

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