Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies
Figure 2
Organization and composition of the dystrophin/utrophin-associated glycoprotein complexes (DGC/UGC). The NH2-terminus of dystrophins and utrophins (purple) binds to cytoskeletal filamentous actin (F-actin) while the cysteine-rich and COOH domains interact with the different DGC/UGC components. The cysteine-rich domain binds the dystroglycan subcomplex composed of transmembrane -dystroglycan (-DG) and extracellular -dystroglycan (-DG). The -dystroglycan may interact with the sarcoglycan-sarcospan subcomplex (blue) and with signaling protein such as Grb2. The -DG is a glycosylated receptor for extracellular matrix proteins, such as laminin, agrin, perlecan, and neurexin depending on tissue- and cell-specific expression. The COOH-terminus of dystrophins/utrophins binds the cytosolic proteins syntrophins and dystrobrevins. Dystrobrevins associate with syncoilin, dysbindin, and syntrophins (SYN). Syntrophins contain a PDZ domain enabling associations of the DGC with a variety of proteins including signaling and synaptic proteins, such as neuronal nitric oxide synthase (nNOS) or neuroligins, as well as several transmembrane channels (AQP-4, potassium Kir2 and Kir4.1, and voltage-gated sodium channels) and receptors (AchR, R).
