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The phospholipid PI(3,4)P2 is an apical identity determinant

Author

Listed:
  • Álvaro Román-Fernández

    (University of Glasgow
    The CRUK Beatson Institute)

  • Julie Roignot

    (University of California
    University of California
    Broad Institute of MIT and Harvard)

  • Emma Sandilands

    (University of Glasgow
    The CRUK Beatson Institute)

  • Marisa Nacke

    (University of Glasgow
    The CRUK Beatson Institute)

  • Mohammed A. Mansour

    (University of Glasgow
    Tanta University)

  • Lynn McGarry

    (The CRUK Beatson Institute)

  • Emma Shanks

    (The CRUK Beatson Institute)

  • Keith E. Mostov

    (University of California
    University of California)

  • David M. Bryant

    (University of Glasgow
    The CRUK Beatson Institute)

Abstract

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.

Suggested Citation

  • Álvaro Román-Fernández & Julie Roignot & Emma Sandilands & Marisa Nacke & Mohammed A. Mansour & Lynn McGarry & Emma Shanks & Keith E. Mostov & David M. Bryant, 2018. "The phospholipid PI(3,4)P2 is an apical identity determinant," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07464-8
    DOI: 10.1038/s41467-018-07464-8
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    Cited by:

    1. Sergi Marco & Matthew Neilson & Madeleine Moore & Arantxa Perez-Garcia & Holly Hall & Louise Mitchell & Sergio Lilla & Giovani R. Blanco & Ann Hedley & Sara Zanivan & Jim C. Norman, 2021. "Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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