title: Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schaaf
authors.forename: Eric A
authors.initials: EA
authors.lastname: Ortlund
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Tyeryar
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mousley
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Ile
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Garrett
authors.forename: Jihui
authors.initials: J
authors.lastname: Ren
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Woolls
authors.forename: Christian R H
authors.initials: CR
authors.lastname: Raetz
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Redinbo
authors.forename: Vytas A
authors.initials: VA
authors.lastname: Bankaitis
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
chemical_list: D019870:1-Phosphatidylinositol 4-Kinase; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins; C483438:SEC14 protein, S cerevisiae