The phospholipid PI(3,4)P<sub>2</sub> is an apical identity determinant.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30487552.
- Also identified by DOI 10.1038/s41467-018-07464-8 and PMC identifier 6262019.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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)P<sub>2</sub> localization and function is distinct from the basolateral determinant PI(3,4,5)P<sub>3</sub>. PI(3,4)P<sub>2</sub> localizes to the apical surface, and Rab11a-positive apical recycling endosomes. PI(3,4)P<sub>2</sub> 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<sub>2</sub> levels results in defective polarization through subcortical retention of apically destined vesicles at apical membrane initiation sites. We conclude that PI(3,4)P<sub>2</sub> is a determinant of apical membrane identity.
Medical subject headings
- Phosphatidylinositols