Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily
MetadataShow full item record
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. © 2008 Elsevier Inc. All rights reserved.
Showing items related by title, author, creator and subject.
Resurrection of a functional phosphatidylinositol transfer protein from a pseudo-Sec14 scaffold by directed evolutionSchaaf, G.; Dynowski, M.; Mousley, Carl; Shah, S.; Yuan, P.; Winklbauer, E.; De Campos, M.; Trettin, K.; Quinones, M.; Smirnova, T.; Yanagisawa, L.; Ortlund, E.; Bankaitis, V. (2011)Sec14-superfamily proteins integrate the lipid metabolome with phosphoinositide synthesis and signaling via primed presentation of phosphatidylinositol (PtdIns) to PtdIns kinases. Sec14 action as a PtdIns-presentation ...
Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphataseWood, C.; Hung, C.; Huoh, Y.; Mousley, Carl; Stefan, C.; Bankaitis, V.; Ferguson, K.; Burd, C. (2012)In the Golgi apparatus, lipid homeostasis pathways are coordinated with the biogenesis of cargo transport vesicles by phosphatidylinositol 4-kinases (PI4Ks) that produce phosphatidylinositol 4-phosphate (PtdIns4P), a ...
PI3K Class II [alpha] Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium FunctionFranco, I.; Gulluni, F.; Campa, C.; Costa, C.; Margaria, J.; Ciraolo, E.; Martini, M.; Monteyne, D.; De Luca, E.; Germena, G.; Posor, Y.; Maffucci, T.; Marengo, S.; Haucke, V.; Falasca, Marco; Perez-Morga, D.; Boletta, A.; Merlo, G.; Hirsch, E. (2014)Multiple phosphatidylinositol (PtdIns) 3-kinases (PI3Ks) can produce PtdIns3P to control endocytic trafficking, but whether enzyme specialization occurs in defined subcellular locations is unclear. Here, we report that ...