2/29/2024 0 Comments Dp116 sparkle and co![]() These isoforms lack the domain for actin binding but commonly contain the domains for β-dystroglycan binding. Short dystrophin isoforms having molecular masses of 260 kDa (Dp260), 140 kDa (Dp140), 116 kDa (Dp116) and 70–80 kDa (Dp71 or apo-dystrophin-1) are translated from transcripts derived from the 3′ region of the dystrophin gene ( 23– 28). Utrophin (395 kDa) is a homolog of dystrophin and conserves actin- and dystroglycan-binding domains at its N‐and C-terminal regions, respectively ( 19– 22). Utrophin and short isoforms of dystrophin are also expressed in these nonmuscle cells. Until now, no SG complex-like structure has been found in non-contracting cells in spite of attempts to find one ( 17, 18).ĭystroglycan complexes are widely expressed in a variety of nonmuscle cells as well as in muscle cells. It remains important to determine whether or not the SG complex is specific for muscle cells in order to understand the physiological roles of the entire dystrophin–DAP complex as well as the SG complex. On the other hand, besides the structural role, the SG complex was suggested to play a role in scaffolding for signal-transduction cascades ( 12). It is considered that the reinforcement of molecular interactions by the SG complex is essential for protecting the muscle cell membrane against contraction-induced mechanical stress ( 3, 16). Analyses of striated muscles of SG-deficient animals revealed that the SG complex plays a role in reinforcing the molecular linkage from α-dystroglycan to dystrophin through the membrane-spanning β-dystroglycan ( 13– 15). Four SGs, α, β-, γ- and δ-SG, comprise a heterotetramer complex that is tightly associated with the dystroglycan complex and SPN ( 4, 10– 12). α-Dystroglycan tightly binds to laminin ( 9), a major component of the basal lamina, indicating that dystrophin and the dystroglycan complex form a cross bridge between the extracellular matrix (ECM) and the actin-based cytoskeletal network. Dystrophin associates with the muscle sarcolemma via β-dystroglycan, which in turn binds to α-dystroglycan ( 4, 7, 8). The latter two domains bind to transmembranous β-dystroglycan, intercellular syntrophins and dystrobrevins ( 5– 8). Biochemical analysis with n-octyl β- d-glucoside clearly showed that the complicated complex was divided into two glycoprotein subcomplexes, namely the dystroglycan and SG complexes, and a cytoplasmic protein subcomplex consisting of dystrophin and dystrophin-associated cytoplasmic proteins (syntrophins and dystrobrevins) ( 4).ĭystrophin, a gene product responsible for Duchenne muscular dystrophy, is a 427 kDa protein composed of four domains: an N-terminal actin-binding domain, a large rod domain, a cysteine-rich domain and a C-terminal domain. This multi-protein complex consists of dystrophin, α- and β-dystroglycan, α-, β-, γ- and δ-sarcoglycan (SG), sarcospan (SPN), syntrophins and dystrobrevins ( 1– 3). The dystrophin–dystrophin-associated protein (DAP) complex, a large membrane protein complex, is critical for the stability of the striated muscle cell membrane. ![]() Received 4 September 2000 Revised and Accepted 20 October 2000. These results demonstrated that Dp116 and utrophin are anchored to a novel membrane protein architecture, which consists of the SG and dystroglycan complexes, but not SPN, in the Schwann cell membrane. An immunoprecipitation study indicated that the SG complex is associated with the dystroglycan complex and Dp116 or utrophin. This observation suggests that the ε-, β- and δ-SG molecules form a complex behaving as a single unit similar to the SG complex in muscle cells. Immunocytochemical analysis using SG-deficient animals showed that a defect in β- or δ-SG led to a great reduction of all residual SGs, but not of the other proteins, i.e., dystroglycans, Dp116 and utrophin, in the peripheral nerve. These peripheral nerve SGs were colocalized at the outermost layer of the myelin sheath of nerve fibers together with the dystroglycan complex, utrophin, and a short dystrophin isoform (Dp116). SPN, which tightly links to the SG complex in the muscle cell membrane, was absent in the peripheral nerve. We found that β-SG and δ-SG were co-expressed with ε-SG, a α-SG homolog, in the peripheral nerve, but not with α-SG or γ-SG. ![]() The SG complex consists of four transmembrane glycoproteins, α-SG, β-SG, γ-SG and δ-SG. ![]() The dystrophin-associated membrane-integrated protein complex anchors dystrophin in the sarcolemma of striated muscles and is composed of two glycoprotein subcomplexes, the dystroglycan and the sarcoglycan (SG) complexes, and a small membrane protein termed sarcospan (SPN).
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