title: An association between type Iγ PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization.
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.
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA.
authors: Xunhao
authors: X
authors: Xiong
authors: Qingwen
authors: Q
authors: Xu
authors: Yan
authors: Y
authors: Huang
authors: Raman Deep
authors: RD
authors: Singh
authors: Richard
authors: R
authors: Anderson
authors: Edward
authors: E
authors: Leof
authors: Jinghua
authors: J
authors: Hu
authors: Kun
authors: K
authors: Ling
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D048430:Cell Shape; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021381:Protein Transport; D051381:Rats; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; C547754:EXOC7 protein, human; D018129:Phosphatidylinositol Phosphates; D033921:Vesicular Transport Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase