title: PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity.
abstract: Plasma membrane phosphatidylinositol (PI) 4-phosphate (PtdIns4P) has critical functions via both direct interactions and metabolic conversion to PI 4,5-bisphosphate (PtdIns(4,5)P₂) and other downstream metabolites. However, mechanisms that control this PtdIns4P pool in cells of higher eukaryotes remain elusive. PI4KIIIα, the enzyme thought to synthesize this PtdIns4P pool, is reported to localize in the ER, contrary to the plasma membrane localization of its yeast homologue, Stt4. In this paper, we show that PI4KIIIα was targeted to the plasma membrane as part of an evolutionarily conserved complex containing Efr3/rolling blackout, which we found was a palmitoylated peripheral membrane protein. PI4KIIIα knockout cells exhibited a profound reduction of plasma membrane PtdIns4P but surprisingly only a modest reduction of PtdIns(4,5)P₂ because of robust up-regulation of PtdIns4P 5-kinases. In these cells, however, much of the PtdIns(4,5)P₂ was localized intracellularly, rather than at the plasma membrane as in control cells, along with proteins typically restricted to this membrane, revealing a major contribution of PI4KIIIα to the definition of plasma membrane identity.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Fubito
authors.initials: F
authors.lastname: Nakatsu
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Baskin
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Chung
authors.forename: Lukas B
authors.initials: LB
authors.lastname: Tanner
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Michelle
authors.initials: M
authors.lastname: Pirruccello
authors.forename: Mingming
authors.initials: M
authors.lastname: Hao
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ingolia
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D018274:Electroporation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015778:Minor Histocompatibility Antigens; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase