The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions

J Biol Chem. 2007 Mar 30;282(13):9392-9400. doi: 10.1074/jbc.M610002200. Epub 2007 Jan 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Discs Large Homolog 1 Protein
  • Dogs
  • Humans
  • Intercellular Junctions / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology*
  • Multigene Family / physiology
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / physiology*
  • Oncogene Proteins, Viral / chemistry
  • Oncogene Proteins, Viral / physiology
  • Protein Transport / physiology
  • Vesicular Transport Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • E6 protein, Human papillomavirus type 6
  • LIN7A protein, human
  • LIN7C protein, human
  • MPP7 protein, human
  • Membrane Proteins
  • Multiprotein Complexes
  • Oncogene Proteins, Viral
  • Vesicular Transport Proteins