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

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,...

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Bibliographic Details
Published in:Nature communications 2018-11, Vol.9 (1), p.1-17, Article 5041
Main Authors: Román-Fernández, Álvaro, Roignot, Julie, Sandilands, Emma, Nacke, Marisa, Mansour, Mohammed A., McGarry, Lynn, Shanks, Emma, Mostov, Keith E., Bryant, David M.
Format: Article
Language:English
Subjects:
13/1
13/106
13/95
14/10
14/35
14/63
49/56
631/136/1660
631/80/313
631/80/85/2361
631/80/86/2364
Asymmetry
Biochemistry
Cortex
Cysts
Embedding
Endosomes
Epithelial cells
Extracellular matrix
Humanities and Social Sciences
Inositol-1,4,5-trisphosphate 5-phosphatase
Kinases
Lipids
Localization
Membrane vesicles
Membranes
multidisciplinary
Phosphatase
Phosphatidylinositol 3,4,5-triphosphate
Phospholipids
Polarization
Protein turnover
Proteins
Science
Science (multidisciplinary)
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Summary: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)P 2 localization and function is distinct from the basolateral determinant PI(3,4,5)P 3 . PI(3,4)P 2 localizes to the apical surface, and Rab11a-positive apical recycling endosomes. PI(3,4)P 2 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)P 2 levels results in defective polarization through subcortical retention of apically destined vesicles at apical membrane initiation sites. We conclude that PI(3,4)P 2 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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-07464-8