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PMID: 22075145 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

A highly dynamic ER-derived phosphatidylinositol-synthesizing organelle supplies phosphoinositides to cellular membranes.

Developmental cell ·Vol. 21 ·No. 5 ·2011-11-15 ·Pages 813-24

Kim YJ, Guzman-Hernandez ML, Balla T

Abstract

Polyphosphoinositides are lipid signaling molecules generated from phosphatidylinositol (PtdIns) with critical roles in vesicular trafficking and signaling. It is poorly understood where PtdIns is located within cells and how it moves around between membranes. Here we identify a hitherto-unrecognized highly mobile membrane compartment as the site of PtdIns synthesis and a likely source of PtdIns of all membranes. We show that the PtdIns-synthesizing enzyme PIS associates with a rapidly moving compartment of ER origin that makes ample contacts with other membranes. In contrast, CDP-diacylglycerol synthases that provide PIS with its substrate reside in the tubular ER. Expression of a PtdIns-specific bacterial PLC generates diacylglycerol also in rapidly moving cytoplasmic objects. We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to other membranes during multiple contacts by yet-to-be-defined lipid transfer mechanisms.

MeSH Terms
Animals COS Cells Cell Membrane/chemistry,metabolism Chlorocebus aethiops Diacylglycerol Cholinephosphotransferase/chemistry,metabolism Endoplasmic Reticulum/chemistry,enzymology,metabolism HEK293 Cells Humans Organelles/chemistry,metabolism Phosphatidylinositols/biosynthesis,chemistry,metabolism Signal Transduction
Chemicals
Phosphatidylinositols Diacylglycerol Cholinephosphotransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kim Yeun Ju
Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
Guzman-Hernandez Maria Luisa
Balla Tamas
References (48)
48 references, click to expand
  1. Isolation and chromosomal localization of two human CDP-diacylglycerol synthase (CDS) genes.
    Genomics. 1998 Nov 15;54(1):140-4 PMID: 9806839
  2. ARF family G proteins and their regulators: roles in membrane transport, development and disease.
    Nat Rev Mol Cell Biol. 2011 Jun;12(6):362-75 PMID: 21587297
  3. Inositol phospholipids and cell surface receptor function.
    Biochim Biophys Acta. 1975 Mar 25;415(1):81-47 PMID: 164246
  4. Phosphatidylinositol synthase is required for lens structural integrity and photoreceptor cell survival in the zebrafish eye.
    Exp Eye Res. 2011 Oct;93(4):460-74 PMID: 21722635
  5. Characteristics of rat liver phosphatidylinositol kinase and its presence in the plasma membrane.
    Biochim Biophys Acta. 1967 Dec 5;144(3):649-58 PMID: 4294903
  6. An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
    Nat Methods. 2005 Jun;2(6):415-8 PMID: 15908919
  7. Synaptic defects and compensatory regulation of inositol metabolism in inositol polyphosphate 1-phosphatase mutants.
    Neuron. 1998 Jun;20(6):1219-29 PMID: 9655509
  8. The enzymatic synthesis of inositol phosphatide.
    J Biol Chem. 1958 Nov;233(5):1077-83 PMID: 13598735
  9. A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5317-21 PMID: 7777504
  10. Phosphatidylinositol synthase from yeast.
    Biochim Biophys Acta. 1997 Sep 4;1348(1-2):173-8 PMID: 9370330
  11. The inhibition of phosphoinositide synthesis and muscarinic-receptor-mediated phospholipase C activity by Li+ as secondary, selective, consequences of inositol depletion in 1321N1 cells.
    Biochem J. 1994 Feb 1;297 ( Pt 3):529-37 PMID: 8110190
  12. Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells.
    J Cell Biol. 1998 Feb 9;140(3):485-98 PMID: 9456311
  13. Direct imaging shows that insulin granule exocytosis occurs by complete vesicle fusion.
    Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9266-71 PMID: 15197259
  14. The role of CDP-diacylglycerol synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content.
    J Biol Chem. 1997 Dec 26;272(52):33402-9 PMID: 9407135
  15. Mutagenesis of active-site histidines of Listeria monocytogenes phosphatidylinositol-specific phospholipase C: effects on enzyme activity and biological function.
    Infect Immun. 1999 Jan;67(1):182-6 PMID: 9864213
  16. Function of the phosphatidylinositol transfer protein gene family: is phosphatidylinositol transfer the mechanism of action?
    Crit Rev Biochem Mol Biol. 2011 Apr;46(2):89-117 PMID: 21275878
  17. Phosphatidylinositol transfer proteins and cellular nanoreactors for lipid signaling.
    Nat Chem Biol. 2006 Nov;2(11):576-83 PMID: 17051233
  18. Bacterial phosphatidylinositol-specific phospholipase C: structure, function, and interaction with lipids.
    Biochim Biophys Acta. 1999 Nov 23;1441(2-3):237-54 PMID: 10570252
  19. Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish.
    Hepatology. 2011 Aug;54(2):452-62 PMID: 21488074
  20. Visualization and manipulation of plasma membrane-endoplasmic reticulum contact sites indicates the presence of additional molecular components within the STIM1-Orai1 Complex.
    J Biol Chem. 2007 Oct 5;282(40):29678-90 PMID: 17684017
  21. A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.
    J Biol Chem. 2007 Jan 12;282(2):826-30 PMID: 17071619
  22. A photoactivatable GFP for selective photolabeling of proteins and cells.
    Science. 2002 Sep 13;297(5588):1873-7 PMID: 12228718
  23. Subcellular localization of phosphatidylinositol synthesis.
    Biochem Biophys Res Commun. 2006 Sep 29;348(3):1200-4 PMID: 16904631
  24. Disruption by lithium of phosphatidylinositol-4,5-bisphosphate supply and inositol-1,4,5-trisphosphate generation in Chinese hamster ovary cells expressing human recombinant m1 muscarinic receptors.
    Mol Pharmacol. 1994 Dec;46(6):1138-48 PMID: 7808434
  25. Effects of acetylcholine on the turnover of phosphoryl units in individual phospholipids of pancreas slices and brain cortex slices.
    Biochim Biophys Acta. 1955 Sep;18(1):102-10 PMID: 13260248
  26. Phosphoinositide signaling: new tools and insights.
    Physiology (Bethesda). 2009 Aug;24:231-44 PMID: 19675354
  27. Independent phosphatidylinositol synthesis in pituitary plasma membrane and endoplasmic reticulum.
    Nature. 1987 Feb 19-25;325(6106):726-8 PMID: 3029593
  28. Visualization of cellular phosphoinositide pools with GFP-fused protein-domains.
    Curr Protoc Cell Biol. 2009 Mar;Chapter 24:Unit 24.4 PMID: 19283730
  29. Mammalian phosphoinositide kinases and phosphatases.
    Prog Lipid Res. 2009 Nov;48(6):307-43 PMID: 19580826
  30. Phosphatidylinositol synthase from yeast.
    Methods Enzymol. 1992;209:305-12 PMID: 1323046
  31. Subcellular distribution of agonist-stimulated phosphatidylinositol synthesis in 1321 N1 astrocytoma cells.
    Biochem J. 1993 Mar 1;290 ( Pt 2):381-7 PMID: 8452524
  32. Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity on GPI anchors.
    Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12927-31 PMID: 16118276
  33. Cloning of CDP-diacylglycerol synthase from a human neuronal cell line.
    J Neurochem. 1996 Nov;67(5):2200-3 PMID: 8863531
  34. Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites.
    Cell. 2011 Feb 4;144(3):389-401 PMID: 21295699
  35. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells.
    EMBO J. 2000 Sep 1;19(17):4577-88 PMID: 10970851
  36. Subcellular distribution of the PI effect in the pancreas of the guinea pig.
    Life Sci. 1974 Aug 15;15(4):711-21 PMID: 4549938
  37. The molecular choreography of a store-operated calcium channel.
    Nature. 2007 Mar 15;446(7133):284-7 PMID: 17361175
  38. Immunocytochemical techniques reveal multiple, distinct cellular pools of PtdIns4P and PtdIns(4,5)P(2).
    Biochem J. 2009 Jul 29;422(1):23-35 PMID: 19508231
  39. Stimulation by acetylcholine of phosphatidylinositol labelling. Subcellular distribution in rat cerebral-cortex slices.
    Biochem J. 1972 Mar;126(5):1141-7 PMID: 4342207
  40. Regulation of PLC-mediated signalling in vivo by CDP-diacylglycerol synthase.
    Nature. 1995 Jan 19;373(6511):216-22 PMID: 7816135
  41. Biochemical and biological functions of class I phosphatidylinositol transfer proteins.
    Biochim Biophys Acta. 2007 Jun;1771(6):677-91 PMID: 17490911
  42. Probing phosphoinositide functions in signaling and membrane trafficking.
    Trends Cell Biol. 2005 May;15(5):259-68 PMID: 15866030
  43. Functional analysis of mutations in the PIS gene, which encodes Saccharomyces cerevisiae phosphatidylinositol synthase.
    FEMS Microbiol Lett. 1995 Feb 1;126(1):81-4 PMID: 7896081
  44. Multiple pathways of inositol polyphosphate metabolism in angiotensin-stimulated adrenal glomerulosa cells.
    J Biol Chem. 1988 Mar 25;263(9):4083-91 PMID: 3257963
  45. Molecular cloning of rat phosphatidylinositol synthase cDNA by functional complementation of the yeast Saccharomyces cerevisiae pis mutation.
    FEBS Lett. 1996 Sep 9;393(1):89-92 PMID: 8804431
  46. Yeast mutant defective in synthesis of phosphatidylinositol. Isolation and characterization of a CDPdiacylglycerol--inositol 3-phosphatidyltransferase Km mutant.
    Eur J Biochem. 1982 Jul;125(2):445-51 PMID: 6288375
  47. THE INCORPORATION OF 32P FROM TRIPHOSPHATE INTO POLYPHOSPHOINOSITIDES (GAMMA-32P)ADENOSINE AND PHOSPHATIDIC ACID IN ERYTHROCYTE MEMBRANES.
    Biochim Biophys Acta. 1964 Oct 2;84:563-75 PMID: 14250494
  48. Imaging phosphoinositide dynamics using GFP-tagged protein domains.
    Biol Cell. 2005 Jul;97(7):501-18 PMID: 15966865
Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
Published
2011-11-15
Pages
813-24
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC3235737
Subset
IM
Grants
Intramural NIH HHS · Z01 HD000196-10 · United States
Corrections
CommentIn
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