Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex.
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.
Masuda-Hirata
Maki
M
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Kanazawa-ku, Yokohama, Japan.
Suzuki
Atsushi
A
Amano
Yoshiko
Y
Yamashita
Kazunari
K
Ide
Mariko
M
Yamanaka
Tomoyuki
T
Sakai
Michihiro
M
Imamura
Michihiro
M
Ohno
Shigeo
S
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
D007797:Laminin; D017474:Receptors, Laminin; D049030:Dystroglycans; D017346:Protein Serine-Threonine Kinases