Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions.
Tissue development, differentiation, and physiology require specialized cellular adhesion and signal transduction at sites of cell-cell contact. Scaffolding proteins that tether adhesion molecules, receptors, and intracellular signaling enzymes organize macromolecular protein complexes at cellular junctions to integrate these functions. One family of such scaffolding proteins is the large group of membrane-associated guanylate kinases (MAGUKs). Genetic studies have highlighted critical roles for MAGUK proteins in the development and physiology of numerous tissues from a variety of metazoan organisms. Mutation of Drosophila discs large (dlg) disrupts epithelial septate junctions and causes overgrowth of imaginal discs. Similarly, mutation of lin-2, a related MAGUK in Caenorhabditis elegans, blocks vulval development, and mutation of the postsynaptic density protein PSD-95 impairs synaptic plasticity in mammalian brain. These diverse roles are explained by recent biochemical and structural analyses of MAGUKs, which demonstrate their capacity to assemble well--efined--yet adaptable--protein complexes at cellular junctions.
Funke
Lars
L
Department of Physiology, University of California at San Francisco, California 94143, USA. lfunke@itsa.ucsf.edu
Dakoji
Srikanth
S
Bredt
David S
DS
D017398:Alternative Splicing; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D016764:Cell Polarity; D051528:Guanylate Kinases; D007365:Intercellular Junctions / Q000201:enzymology*; D008954:Models, Biological; D008958:Models, Molecular; D009473:Neuronal Plasticity; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013569:Synapses / Q000201:enzymology; D019108:Tight Junctions / Q000201:enzymology
D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases