title: The acyltransferase LYCAT controls specific phosphoinositides and related membrane traffic.
abstract: Phosphoinositides (PIPs) are key regulators of membrane traffic and signaling. The interconversion of PIPs by lipid kinases and phosphatases regulates their functionality. Phosphatidylinositol (PI) and PIPs have a unique enrichment of 1-stearoyl-2-arachidonyl acyl species; however, the regulation and function of this specific acyl profile remains poorly understood. We examined the role of the PI acyltransferase LYCAT in control of PIPs and PIP-dependent membrane traffic. LYCAT silencing selectively perturbed the levels and localization of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol-3-phosphate and the membrane traffic dependent on these specific PIPs but was without effect on phosphatidylinositol-4-phosphate or biosynthetic membrane traffic. The acyl profile of PI(4,5)P2was selectively altered in LYCAT-deficient cells, whereas LYCAT localized with phosphatidylinositol synthase. We propose that LYCAT remodels the acyl chains of PI, which is then channeled into PI(4,5)P2Our observations suggest that the PIP acyl chain profile may exert broad control of cell physiology.
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.|Graduate Program in Molecular Science, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Leslie N
authors.initials: LN
authors.lastname: Bone
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.|Graduate Program in Molecular Science, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Roya M
authors.initials: RM
authors.lastname: Dayam
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Minhyoung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fairn
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.|Japan Agency for Medical Research and Development-Core Research for Evolutionary Science and Technology, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada rbotelho@ryerson.ca cantonescu@ryerson.ca.|Graduate Program in Molecular Science, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Botelho
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada rbotelho@ryerson.ca cantonescu@ryerson.ca.|Graduate Program in Molecular Science, Ryerson University, Toronto, ON M5B 2K3, Canada.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
authors.forename: Costin N
authors.initials: CN
authors.lastname: Antonescu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism* / Q000502:physiology*; D000217:Acyltransferases / Q000378:metabolism / Q000502:physiology; D018929:Cell Culture Techniques; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases; D021381:Protein Transport / Q000502:physiology; D055213:Retinal Pigment Epithelium
chemical_list: D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C055525:phosphatidylinositol 3-phosphate; C037178:phosphatidylinositol 4-phosphate; D000217:Acyltransferases; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C544777:LCLAT1 protein, human; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases