title: Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins.
abstract: MUPP1 and Patj are both composed of an L27 domain and multiple PDZ domains (13 and 10 domains, respectively) and are localized to tight junctions (TJs) in epithelial cells. Although Patj is known to be responsible for the organization of TJs and epithelial polarity, characterization of MUPP1 is lacking. In this study, we found that MUPP1 and Patj share several binding partners, including JAM1, ZO-3, Pals1, Par6, and nectins (cell-cell adhesion molecules at adherens junctions). MUPP1 and Patj exhibited similar subcellular distributions, and the mechanisms with which they localize to TJs also appear to overlap. Despite these similarities, functional studies have revealed that Patj is indispensable for the establishment of TJs and epithelial polarization, whereas MUPP1 is not. Thus, although MUPP1 and Patj share several molecular properties, their functions are entirely different. We present evidence that the signaling mediated by Pals1, which has a higher affinity for Patj than for MUPP1 and is involved in the activation of the Par6-aPKC complex, is of principal importance for the function of Patj in epithelial cells.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. ada@mfour.med.kyoto-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hamazaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Itoh
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
authors.forename: Mikio
authors.initials: M
authors.lastname: Furuse
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000075983:Nectins; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism; D054731:PDZ Domains; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D062725:Tight Junction Proteins; D019108:Tight Junctions / Q000378:metabolism*; D062825:Zonula Occludens Proteins; D062826:Zonula Occludens-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; C111442:MPDZ protein, human; D008565:Membrane Proteins; D000075983:Nectins; C499657:PARD6A protein, human; C107903:PATJ protein, human; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C569042:TJP1 protein, human; C111873:TJP3 protein, human; D062725:Tight Junction Proteins; C569043:Tjp1 protein, mouse; D062825:Zonula Occludens Proteins; D062826:Zonula Occludens-1 Protein; D009703:Nucleoside-Phosphate Kinase; C501307:MPP5 protein, human