title: Dictyostelium uses ether-linked inositol phospholipids for intracellular signalling.
abstract: Inositol phospholipids are critical regulators of membrane biology throughout eukaryotes. The general principle by which they perform these roles is conserved across species and involves binding of differentially phosphorylated inositol head groups to specific protein domains. This interaction serves to both recruit and regulate the activity of several different classes of protein which act on membrane surfaces. In mammalian cells, these phosphorylated inositol head groups are predominantly borne by a C38:4 diacylglycerol backbone. We show here that the inositol phospholipids of Dictyostelium are different, being highly enriched in an unusual C34:1e lipid backbone, 1-hexadecyl-2-(11Z-octadecenoyl)-sn-glycero-3-phospho-(1'-myo-inositol), in which the sn-1 position contains an ether-linked C16:0 chain; they are thus plasmanylinositols. These plasmanylinositols respond acutely to stimulation of cells with chemoattractants, and their levels are regulated by PIPKs, PI3Ks and PTEN. In mammals and now in Dictyostelium, the hydrocarbon chains of inositol phospholipids are a highly selected subset of those available to other phospholipids, suggesting that different molecular selectors are at play in these organisms but serve a common, evolutionarily conserved purpose.
authors.affiliation: Babraham Biosciences Technology Babraham Research Campus, Cambridge, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clark
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK rrk@mrc-lmb.cam.ac.uk len.stephens@bbsrc.ac.uk phillip.hawkins@babraham.ac.uk.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kay
authors.affiliation: Babraham Biosciences Technology Babraham Research Campus, Cambridge, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kielkowska
authors.affiliation: Babraham Biosciences Technology Babraham Research Campus, Cambridge, UK.
authors.forename: Izabella
authors.initials: I
authors.lastname: Niewczas
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Fets
authors.affiliation: Signalling Programme Babraham Research Campus, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Oxley
authors.affiliation: Signalling Programme Babraham Research Campus, Cambridge, UK rrk@mrc-lmb.cam.ac.uk len.stephens@bbsrc.ac.uk phillip.hawkins@babraham.ac.uk.
authors.forename: Len R
authors.initials: LR
authors.lastname: Stephens
authors.affiliation: Signalling Programme Babraham Research Campus, Cambridge, UK rrk@mrc-lmb.cam.ac.uk len.stephens@bbsrc.ac.uk phillip.hawkins@babraham.ac.uk.
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D004023:Dictyostelium / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D010716:Phosphatidylinositols; D010742:Phospholipid Ethers
keywords: Dictyostelium; PI3K; ether lipids; phosphoinositides; plasmanylinositol