An association between type Iγ PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization.

Publication Type:

Journal Article

Source:

Molecular biology of the cell, Volume 23, Issue 1, p.87-98 (2012)

Keywords:

Adherens Junctionsdigestive disease, digestive deseases Animalsdigestive disease, digestive deseases Cadherinsdigestive disease, digestive deseases Cell Linedigestive disease, digestive deseases Cell Membranedigestive disease, digestive deseases Cell Polaritydigestive disease, digestive deseases Cell Shapedigestive disease, digestive deseases Dogsdigestive disease, digestive deseases Epithelial Cellsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Micedigestive disease, digestive deseases Phosphatidylinositol Phosphatesdigestive disease, digestive deseases Phosphotransferases (Alcohol Group Acceptor)digestive disease, digestive deseases Protein Bindingdigestive disease, digestive deseases Protein Interaction Domains and Motifsdigestive disease, digestive deseases Protein Interaction Mappingdigestive disease, digestive deseases Protein Transportdigestive disease, digestive deseases Ratsdigestive disease, digestive deseases Vesicular Transport Proteins

Abstract:

E-Cadherin-mediated formation of adherens junctions (AJs) is essential for the morphogenesis of epithelial cells. However, the mechanisms underlying E-cadherin clustering and AJ maturation are not fully understood. Here we report that type Iγ phosphatidylinositol-4-phosphate 5-kinase (PIPKIγ) associates with the exocyst via a direct interaction with Exo70, the exocyst subunit that guides the polarized targeting of exocyst to the plasma membrane. By means of this interaction, PIPKIγ mediates the association between E-cadherin and Exo70 and determines the targeting of Exo70 to AJs. Further investigation revealed that Exo70 is necessary for clustering of E-cadherin on the plasma membrane and extension of nascent E-cadherin adhesions, which are critical for the maturation of cohesive AJs. In addition, we observed phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) accumulation at E-cadherin clusters during the assembly of E-cadherin adhesions. PIPKIγ-generated PI4,5P(2) is required for recruiting Exo70 to newly formed E-cadherin junctions and facilitates the assembly and maturation of AJs. These results support a model in which PIPKIγ and PIPKIγ-generated PI4,5P(2) pools at nascent E-cadherin contacts cue Exo70 targeting and orient the tethering of exocyst-associated E-cadherin. This could be an important mechanism that regulates E-cadherin clustering and AJ maturation, which is essential for the establishment of solid, polarized epithelial structures.