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

The phospholipid PI(3,4)P2 is an apical identity determinant
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, 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.
2041-1723
Roignot, Julie
ba284f40-a356-470a-ac57-7008d531994d
Sandilands, Emma
a4296aec-60a3-439b-8ee8-9a2764a20139
Nacke, Marisa
a3188147-2c1b-4e45-8e48-195b54e8c369
Mansour, Mohammed
03d901e1-959e-4c7d-acc6-33c6a4b129f7
McGarry, Lynn
8df0a09e-96f1-4a2f-8ab1-3d5fd222eb7f
Shanks, Emma
15354447-e873-4900-923b-3ed4908b996d
Mostov, Keith E.
702729c4-da84-4565-ad62-f34a65727f1f
Bryant, David M.
4323cff2-3a5f-495e-932d-ad1efad72efe
Roignot, Julie
ba284f40-a356-470a-ac57-7008d531994d
Sandilands, Emma
a4296aec-60a3-439b-8ee8-9a2764a20139
Nacke, Marisa
a3188147-2c1b-4e45-8e48-195b54e8c369
Mansour, Mohammed
03d901e1-959e-4c7d-acc6-33c6a4b129f7
McGarry, Lynn
8df0a09e-96f1-4a2f-8ab1-3d5fd222eb7f
Shanks, Emma
15354447-e873-4900-923b-3ed4908b996d
Mostov, Keith E.
702729c4-da84-4565-ad62-f34a65727f1f
Bryant, David M.
4323cff2-3a5f-495e-932d-ad1efad72efe

Roignot, Julie, Sandilands, Emma, Nacke, Marisa, Mansour, Mohammed, McGarry, Lynn, Shanks, Emma, Mostov, Keith E. and Bryant, David M. (2018) The phospholipid PI(3,4)P2 is an apical identity determinant. Nature Communications, 9. (doi:10.1038/s41467-018-07464-8).

Record type: Article

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.

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Accepted/In Press date: 22 October 2018
Published date: 28 November 2018

Identifiers

Local EPrints ID: 432627
URI: https://eprints.soton.ac.uk/id/eprint/432627
ISSN: 2041-1723
PURE UUID: 7a63da87-485f-400e-94b0-ef87d61f04b7

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Date deposited: 22 Jul 2019 16:30
Last modified: 02 Dec 2019 17:34

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Contributors

Author: Julie Roignot
Author: Emma Sandilands
Author: Marisa Nacke
Author: Lynn McGarry
Author: Emma Shanks
Author: Keith E. Mostov
Author: David M. Bryant

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