Mechanisms of MAGUK-mediated cellular junctional complex organization

Curr Opin Struct Biol. 2018 Feb:48:6-15. doi: 10.1016/j.sbi.2017.08.006. Epub 2017 Sep 14.

Abstract

Membrane-associated guanylate kinases (MAGUKs) are a family of scaffold proteins that are enriched in cellular junctions and essential for tissue development and homeostasis. Mutations of MAGUKs are linked to many human diseases including cancers, psychiatric disorders, and intellectual disabilities. MAGUKs share a common PDZ-SH3-GK tandem domain organization at the C-terminal end. In this review, we summarize the mechanistic basis governing target recognition and regulations of this binding by the PDZ-SH3-GK tandem of various MAGUKs. We also discuss recent discoveries showing unique folding features of MAGUK PDZ-SH3-GK tandems that facilitate ligand-induced oligomerization of MAGUKs and phase transition of MAGUK-assembled synaptic signaling complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Binding Sites
  • Gene Expression
  • Guanylate Kinases / chemistry*
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism*
  • Intellectual Disability / pathology
  • Intercellular Junctions / metabolism*
  • Intercellular Junctions / ultrastructure
  • Models, Molecular
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Psychotic Disorders / genetics
  • Psychotic Disorders / metabolism*
  • Psychotic Disorders / pathology
  • Synapses / metabolism*
  • Synapses / ultrastructure

Substances

  • Guanylate Kinases