Sci. STKE, 12 September 2006
CELL POLARITY Building a Basolateral Surface
The apical and basolateral plasma membranes of polarized epithelial cells are functionally distinct and are composed of different proteins and lipids. Noting that phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], which plays a prominent role in establishing the polarity of cells undergoing chemotaxis, is present in the basolateral but not the apical membranes of polarized epithelial cells, Gassama-Diagne et al. investigated its role in determining epithelial polarity. The authors used histone-PtdIns(3,4,5)P3 complexes to insert exogenous PtdIns(3,4,5)P3 into the apical membranes of cultured Madin-Darby canine kidney (MDCK) cells that expressed a protein in which green fluorescent protein (GFP) was fused to the PtdIns(3,4,5)P3-binding pleckstrin homology domain of Akt (GFP-PH-Akt). About half the treated cells rapidly formed apical protrusions that labeled with GFP-PH-Akt (which did not associate with the apical surface of untreated cells). The protrusions contained abundant F-actin, and their formation was blocked by latrunculin B, which inhibits actin polymerization. Basolateral membrane proteins (syntaxin 4, p58, and Sec8) were found in the protrusions, whereas the apical membrane protein GP135 was not, and biotin labeling indicated that basolateral proteins relocalized to the apical membrane. LY204002 [an inhibitor of phosphatidylinositol 3-kinase (PI3K)] decreased protrusion formation in treated cells, suggesting that exogenous PtdIns(3,4,5)P3 stimulated the production of endogenous PtdIns(3,4,5)P3. Untreated cells grown in the presence of PI3K inhibitors had smaller basolateral surfaces. Thus, the authors conclude that PtdIns(3,4,5)P3, which is involved in determining polarity in chemotaxing cells and neurons, also regulates formation of the basolateral membranes of polarized epithelial cells.
A. Gassama-Diagne, W. Yu, M. ter Beest, F. Martin-Belmonte, A. Kierbel, J. Engel, K. Mostov, Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells. Nat. Cell Biol. 8, 963-970 (2006). [PubMed]
Citation: Building a Basolateral Surface. Sci. STKE 2006, tw311 (2006).
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