title: Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex.
abstract: Cell polarity depends on extrinsic spatial cues and intrinsic polarity proteins including PAR-aPKC proteins. In mammalian epithelial cells, cell-cell contacts provide spatial cues that activate the aPKC-PAR-3-PAR-6 complex to establish the landmark of the initial cellular asymmetry. PAR-1, a downstream target of the aPKC-PAR-3-PAR-6 complex, mediates further development of the apical and basolateral membrane domains. However, the relationships between the PAR-aPKC proteins and other extrinsic spatial cues provided by the extracellular matrix (ECM) remain unclear. Here, we show that PAR-1 colocalizes with laminin receptors and is required for the assembly of extracellular laminin on the basal surface of epithelial cells. Furthermore, PAR-1 regulates the basolateral localization of the dystroglycan (DG) complex, one of the laminin receptors essential for basement membrane formation. We also show that PAR-1 interacts with the DG complex and is required for the formation of a functional DG complex. These results reveal the presence of a novel inside-out pathway in which an intracellular polarity protein regulates the ECM organization required for epithelial cell polarity and tissue morphogenesis.
authors: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Kanazawa-ku, Yokohama, Japan.
authors: Maki
authors: M
authors: Masuda-Hirata
authors: Atsushi
authors: A
authors: Suzuki
authors: Yoshiko
authors: Y
authors: Amano
authors: Kazunari
authors: K
authors: Yamashita
authors: Mariko
authors: M
authors: Ide
authors: Tomoyuki
authors: T
authors: Yamanaka
authors: Michihiro
authors: M
authors: Sakai
authors: Michihiro
authors: M
authors: Imamura
authors: Shigeo
authors: S
authors: Ohno
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D049030:Dystroglycans / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D007797:Laminin / Q000502:physiology*; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism; D014162:Transfection
chemical_list: D007797:Laminin; D017474:Receptors, Laminin; D049030:Dystroglycans; D017346:Protein Serine-Threonine Kinases