Syntrophins and dystrobrevins: defining the dystrophin scaffold at synapses.
Dystrophin and its associated proteins were originally identified in skeletal muscle, where the complex provides mechanical stabilization to the sarcolemma during contraction. However, the dystrophin complex is also present at membrane specializations in many non-muscle cells, including synaptic sites in neurons. The function of the dystrophin complex at these sites is still unknown, but emerging results suggest that the dystrophin complex can function as a scaffold for signaling proteins. In this review, we examine the growing body of evidence that suggests the dystrophin complex may have a dual function: membrane stabilization and transmembrane signaling. We focus on the role of two dystrophin-associated proteins, syntrophin and dystrobrevin, in the formation of a signaling scaffold and review evidence suggesting a role in synapse formation and maintenance.
Department of Physiology and Biophysics, University of Washington, Seattle, 98195, USA.
Douglas E
DE
Albrecht
Stanley C
SC
Froehner
D000818:Animals; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D016189:Dystrophin / Q000502:physiology*; D049029:Dystrophin-Associated Proteins; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D020935:MAP Kinase Signaling System; D046911:Macromolecular Substances; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009479:Neuropeptides / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure*
C490915:DTNA protein, human; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C098885:dystrobrevin; C091824:syntrophin; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I