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We are analyzing https://www.nature.com/articles/s41467-018-07464-8.

Title:
The phospholipid PI(3,4)P2 is an apical identity determinant | Nature Communications
Description:
Apical-basal polarization is essential for epithelial tissue formation, segregating cortical domains to perform distinct physiological functions. Cortical lipid asymmetry has emerged as a determinant of cell polarization. We report a network of phosphatidylinositol phosphate (PIP)-modifying enzymes, some of which are transcriptionally induced upon embedding epithelial cells in extracellular matrix, and that are essential for apical-basal polarization. Unexpectedly, we find that PI(3,4)P2 localization and function is distinct from the basolateral determinant PI(3,4,5)P3. PI(3,4)P2 localizes to the apical surface, and Rab11a-positive apical recycling endosomes. PI(3,4)P2 is produced by the 5-phosphatase SHIP1 and Class-II PI3-Kinases to recruit the endocytic regulatory protein SNX9 to basolateral domains that are being remodeled into apical surfaces. Perturbing PI(3,4)P2 levels results in defective polarization through subcortical retention of apically destined vesicles at apical membrane initiation sites. We conclude that PI(3,4)P2 is a determinant of apical membrane identity. During de novo establishment of apical-basal polarity, a basolateral membrane must be converted into an apical delivery zone. Here, the authors use MDCK 3D cysts to uncover that the phospholipid PI(3,4)P2 is an apical membrane determinant.
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Keywords {🔍}

pip, apical, fig, cysts, lumen, article, cell, formation, ship, arrowheads, cells, basolateral, podxl, google, scholar, cas, mdck, polarity, amis, experiments, polarization, white, control, independent, supplementary, analysis, localization, membrane, vesicles, red, wellsconditionexperiment, nature, raba, inverted, yellow, snx, stained, image, epithelial, quantitation, figure, domain, cyst, expressing, cortical, blue, depletion, biol, images, egfpxphtapp,

Topics {✒️}

nature portfolio privacy policy org/tools/protocols/plko/ rnai-resistant wild-type mcherry-snx9 par3-positive/pip3-depleted zone expanded advertising mutant egfp-2xph-tapp1 unable expressing egfp-2xph-tapp1 [pi class-ii pi3-kinases contribute social media actin-mediated endocytic trafficking class-ii pi3-kinases pik3c2a/ perform high-resolution z-stacks expressing egfp-2xph-tapp1 reprints validated egfp-2xph-tapp1 egfp-2xph-tapp1 r211l p2 [egfp-2xph-tapp1] localization podxl/pip reporter-positive vesicles nature 552 nature 517 nature 499 nature egfp-2xph-tapp1 probe class-ii pi3-kinases24 phosphoinositide binding-deficient mutant class-ii pi3-kinases thermo fisher scientific ship1-egfp phosphatase-dead cells pip3 [egfp-ph-grp1] localization pip-binding defective mutants gfp-tagged pip reporters pip-modifying enzyme expression stably expressing gfp-pik3c2a pip-binding defective mutant apical apkc/cdc42/par3 complex gfp-anx2 relative intensity de novo generation sec14-nodulin domain protein single-mdck cells divide type i-kinases inhibitor de novo polarization rab11a-positive vesicles rearranged multiple lumens/vesicular accumulation semi-automated polarity analysis open lumen stages pi 3-kinase-dependent pathway lumen de novo constitutively rab11a-endosome adjacent podxl-positive vesicular compartments

Questions {❓}

  • How is PI(3,4)P2 generated?
  • If PI(3,4)P2 is both in recycling endosomes and the apical domain, how can it be an apical determinant?
  • Specifically, what controls cell–cell contact remodeling into an AMIS?
  • What is the function of apical PI(3,4)P2 in 3D polarization?

Schema {🗺️}

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      headline:The phospholipid PI(3,4)P2 is an apical identity determinant
      description:Apical-basal polarization is essential for epithelial tissue formation, segregating cortical domains to perform distinct physiological functions. Cortical lipid asymmetry has emerged as a determinant of cell polarization. We report a network of phosphatidylinositol phosphate (PIP)-modifying enzymes, some of which are transcriptionally induced upon embedding epithelial cells in extracellular matrix, and that are essential for apical-basal polarization. Unexpectedly, we find that PI(3,4)P2 localization and function is distinct from the basolateral determinant PI(3,4,5)P3. PI(3,4)P2 localizes to the apical surface, and Rab11a-positive apical recycling endosomes. PI(3,4)P2 is produced by the 5-phosphatase SHIP1 and Class-II PI3-Kinases to recruit the endocytic regulatory protein SNX9 to basolateral domains that are being remodeled into apical surfaces. Perturbing PI(3,4)P2 levels results in defective polarization through subcortical retention of apically destined vesicles at apical membrane initiation sites. We conclude that PI(3,4)P2 is a determinant of apical membrane identity. During de novo establishment of apical-basal polarity, a basolateral membrane must be converted into an apical delivery zone. Here, the authors use MDCK 3D cysts to uncover that the phospholipid PI(3,4)P2 is an apical membrane determinant.
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         Membrane trafficking
         Morphogenesis
         Phosphoinositol signalling
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         multidisciplinary
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      url:http://orcid.org/0000-0002-5032-3460
      affiliation:
            name:University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      name:Julie Roignot
      affiliation:
            name:University of California
            address:
               name:Department of Anatomy, University of California, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:University of California
            address:
               name:Department of Biochemistry and Biophysics, University of California, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Emma Sandilands
      url:http://orcid.org/0000-0001-6829-0911
      affiliation:
            name:University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      name:Marisa Nacke
      affiliation:
            name:University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      name:Mohammed A. Mansour
      url:http://orcid.org/0000-0001-8701-4007
      affiliation:
            name:University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:Tanta University
            address:
               name:Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
               type:PostalAddress
            type:Organization
      name:Lynn McGarry
      url:http://orcid.org/0000-0002-7055-2615
      affiliation:
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      name:Emma Shanks
      affiliation:
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      name:Keith E. Mostov
      url:http://orcid.org/0000-0002-8123-6247
      affiliation:
            name:University of California
            address:
               name:Department of Anatomy, University of California, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:University of California
            address:
               name:Department of Biochemistry and Biophysics, University of California, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:David M. Bryant
      url:http://orcid.org/0000-0003-2721-5012
      affiliation:
            name:University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:The CRUK Beatson Institute
            address:
               name:The CRUK Beatson Institute, Glasgow, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:The CRUK Beatson Institute, Glasgow, UK
      name:Department of Anatomy, University of California, San Francisco, USA
      name:Department of Biochemistry and Biophysics, University of California, San Francisco, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:The CRUK Beatson Institute, Glasgow, UK
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:The CRUK Beatson Institute, Glasgow, UK
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
      name:The CRUK Beatson Institute, Glasgow, UK
      name:The CRUK Beatson Institute, Glasgow, UK
      name:Department of Anatomy, University of California, San Francisco, USA
      name:Department of Biochemistry and Biophysics, University of California, San Francisco, USA
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:The CRUK Beatson Institute, Glasgow, UK

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