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

Xunhao Xiong, Qingwen Xu, Yan Huang, Raman Deep Singh, Richard Anderson, Edward Leof, Jinghua Hu, Kun Ling

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 PI4,5P2 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 PI4,5P2 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.

Original languageEnglish (US)
Pages (from-to)87-98
Number of pages12
JournalMolecular biology of the cell
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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