University of Dundee

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

Event Date: 
Thursday, April 11, 2019 - 14:00 to 15:00
Event Location: 
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Host: 
Dr David Murray
Event Speaker: 
Dr David Bryant
Institution: 
Institute of Cancer Sciences / CRUK Beatson Institute University of Glasgow
Event Type: 
Seminar
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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.