TY - JOUR
T1 - The phospholipid PI (3, 4) P 2 is an apical identity determinant
AU - Román-Fernández, Álvaro
AU - Roignot, Julie
AU - Sandilands, Emma
AU - Nacke, Marisa
AU - Mansour, Mohammed A.
AU - McGarry, Lynn
AU - Shanks, Emma
AU - Mostov, Keith E.
AU - Bryant, David M.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/11/28
Y1 - 2018/11/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85057559974&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07464-8
DO - 10.1038/s41467-018-07464-8
M3 - Article
SN - 2041-1723
VL - 9
SP - 1
EP - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5041
ER -