Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily

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• 作者：Gabriel Schaaf ; Eric A. Ortlund ; Kimberly R. Tyeryar ; Carl J. Mousley ; Kristina E. Ile ; Teresa A. Garrett ; Jihui Ren ; Melissa J. Woolls ; Christian R.H. Raetz ; Matthew R. Redinbo ; Vytas A. Bankaitis
• 关键词：DNA
• 刊名：Molecular Cell
• 出版年：2008
• 出版时间：1 February 2008
• 年：2008
• 卷：29
• 期：2
• 页码：191-206
• 全文大小：2718 K

文摘

Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at distinct (but overlapping) sites, and both PtdIns- and PtdCho-binding activities are essential Sec14 activities. We further show both activities must reside within the same molecule to reconstitute a functional Sec14 and for effective Sec14-mediated regulation of phosphoinositide homeostasis in vivo. This regulation is uncoupled from PtdIns-transfer activity and argues for an interfacial presentation mode for Sec14-mediated potentiation of PtdIns kinases. Such a regulatory role for Sec14 is a primary counter to action of the Kes1 sterol-binding protein that antagonizes PtdIns 4-OH kinase activity in vivo. Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes.