title: The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions.
abstract: MPP7, a previously uncharacterized member of the p55 Stardust family of membrane-associated guanylate kinase (MAGUK) proteins, was found in a tripartite complex with DLG1 and LIN7A or LIN7C. MPP7 dimerizes with all three LIN7 family members (LIN7A, -B, and -C) through interaction of the single L27 domain of LIN7 with the carboxyl-terminal L27 domain of MPP7, thereby stabilizing both proteins. The dimer of MPP7 with LIN7A or LIN7C associates with DLG1 through an interaction requiring the amino-terminal L27 domain of MPP7. The amino-terminal L27 domain of MPP7 is not sufficient for interaction with DLG1 but interacts efficiently only if MPP7 is in a complex with LIN7A or -C. Thus the specificity of interaction of DLG1 with the LIN7-MPP7 complex is determined by L27 interactions with both MPP7 and LIN7. The tripartite complex forms in a ratio of 1:1:1 and localizes to epithelial adherens junctions in a manner dependent upon MPP7. Expression of MPP7 stabilizes DLG1 in an insoluble compartment. Expression of MPP7 deleted of the PDZ or Src homology 3 domain redistributes MPP7, DLG1, and LIN7 out of adherens junctions and into the soluble cytoplasmic fraction without changing the localization of E-cadherin. Thus, the stability and localization of DLG1 to cell-cell junctions are complex functions determined by the expression and association of particular Stardust family members together with particular LIN7 family members.
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors.forename: Joanna
authors.initials: J
authors.lastname: Bohl
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brimer
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors.forename: Charles
authors.initials: C
authors.lastname: Lyons
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908. Electronic address: vandepol@virginia.edu.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Vande Pol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D000074288:Discs Large Homolog 1 Protein; D004285:Dogs; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D005810:Multigene Family / Q000502:physiology; D046912:Multiprotein Complexes / Q000737:chemistry / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D033921:Vesicular Transport Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C118860:E6 protein, Human papillomavirus type 6; C486532:LIN7A protein, human; C486531:LIN7C protein, human; C482290:MPP7 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009856:Oncogene Proteins, Viral; D033921:Vesicular Transport Proteins