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

Román-Fernández, Á. , Roignot, J., Sandilands, E., Nacke, M., Mansour, M. A., McGarry, L., Shanks, E., Mostov, K. E. and Bryant, D. M. (2018) The phospholipid PI(3,4)P2 is an apical identity determinant. Nature Communications, 9, 5041. (doi: 10.1038/s41467-018-07464-8) (PMID:30487552) (PMCID:PMC6262019)

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.

• Item Type: Articles
• Additional Information: Supported by NIH grants R01DK074398 and R01DK091530 and Baltimore Polycystic Kidney Disease Research and Clinical Core Center P30 DK090868 (K.M.), CRUK C596/A17196 (E.S.), and NIH K99CA163535 (D.B.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roman Fernandez, Mr Alvaro and Mansour, Dr Mohammed Ahmed and Nacke, Marisa and Shanks, Dr Emma and McGarry, Ms Lynn and Bryant, Dr David and Sandilands, Dr Emma
• Authors: Román-Fernández, Á., Roignot, J., Sandilands, E., Nacke, M., Mansour, M. A., McGarry, L., Shanks, E., Mostov, K. E., and Bryant, D. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Nature Communications 9: 5041
• Publisher Policy: Reproduced under a Creative Commons License