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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism
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Cell Line
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Nectins
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Nucleoside-Phosphate Kinase / genetics
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Nucleoside-Phosphate Kinase / metabolism
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PDZ Domains*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Binding
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RNA Interference
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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Tight Junction Proteins
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Tight Junctions / metabolism*
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Zonula Occludens Proteins
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Zonula Occludens-1 Protein
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Adhesion Molecules
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F11R protein, human
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MPDZ protein, human
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Membrane Proteins
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Nectins
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PARD6A protein, human
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PATJ protein, human
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Phosphoproteins
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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TJP1 protein, human
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TJP3 protein, human
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Tight Junction Proteins
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Tjp1 protein, mouse
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Zonula Occludens Proteins
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Zonula Occludens-1 Protein
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Nucleoside-Phosphate Kinase
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MPP5 protein, human