Dystrophin-glycoprotein complex

Sunada, Yoshihide; Campbell, Kevin P.

doi:10.1097/00019052-199510000-00010

Cited by 71 publications

(12 citation statements)

References 48 publications

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“…Duchenne and Becker muscular dystrophies are X-linked disorders caused by mutation or deletion of dystrophin (51). We have found that deletion of dystrophin in the mdx mouse causes a shift in Ca 2ϩ channel voltage dependence toward more positive potentials and reduces channel potentiation.…”

Section: Effects Of Pka On Voltage Dependence Of Ca 2؉ Channel Activimentioning

confidence: 95%

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson

Scheuer

Catterall

2005

Proc. Natl. Acad. Sci. U.S.A.

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The skeletal muscle L-type Ca 2؉ channel (CaV1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltagedependent manner that requires direct physical association between the channel and the kinase mediated through A-kinase anchoring proteins (AKAPs). The role of the actin cytoskeleton in channel regulation was investigated in skeletal myocytes cultured from wild-type mice, mdx mice that lack the cytoskeletal linkage protein dystrophin, and a skeletal muscle cell line, 129 CB 3. Voltage dependence of channel activation was shifted positively, and potentiation was greatly diminished in mdx myocytes and in 129 CB 3 cells treated with the microfilament stabilizer phalloidin. Voltage-dependent potentiation by strong depolarizing prepulses was reduced in mdx myocytes but could be restored by positively shifting the stimulus potentials to compensate for the positive shift in the voltage dependence of gating. Inclusion of PKA in the pipette caused a negative shift in the voltage dependence of activation and restored voltage-dependent potentiation in mdx myocytes. These results show that skeletal muscle Ca 2؉ channel activity and voltage-dependent potentiation are controlled by PKA and microfilaments in a convergent manner. Regulation of Ca 2؉ channel activity by hormones and neurotransmitters that use the PKA signal transduction pathway may interact in a critical way with the cytoskeleton and may be impaired by deletion of dystrophin, contributing to abnormal regulation of intracellular calcium concentrations in dystrophic muscle.calcium channel ͉ protein phosphorylation ͉ muscular dystrophy V oltage-gated Ca 2ϩ channels present in most cells play a critical role in converting cellular electrical activity into an intracellular Ca 2ϩ signal. Neurotransmitter and hormone release from neurons and endocrine cells, gene expression in many cell types, and contraction of cardiac, smooth, and skeletal muscle are all dependent on the activity of voltage-gated Ca 2ϩ channels. In skeletal muscle cells, the Ca V 1.1 channels in transverse tubules have two distinct functional roles. They serve as the voltage sensor for excitation-contraction coupling and transduce a voltage-dependent conformational change into activation of the ryanodine-sensitive Ca 2ϩ release channels in the sarcoplasmic reticulum (1, 2). Ca 2ϩ release from the sarcoplasmic reticulum rapidly initiates contraction. In addition, on a slower time scale, the L-type Ca 2ϩ current conducted by these channels is activated, and the resulting Ca 2ϩ influx increases contractile force in subsequent contractions (3, 4) and regulates gene expression and other muscle activities (5).Activation of skeletal muscle Ca 2ϩ channels is increased by cAMP-dependent phosphorylation in response to adrenergic stimulation (3, 6) and is further potentiated by strong depolarization (7-9), which requires cAMP-dependent protein kinase (PKA) phosphorylation (7). PKA is often anchored near substrates by A-kinas...

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Section: Effects Of Pka On Voltage Dependence Of Ca 2؉ Channel Activimentioning

confidence: 95%

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson

Scheuer

Catterall

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…1 is critical to the stability of muscle fiber membranes (1,2). Components of the DGC include several cytoplasmic proteins (for example dystrophin and the syntrophins) and two subcomplexes (3) of transmembrane glycoproteins, the dystroglycans (␣ and ␤; Ref.…”

Section: A Group Of Proteins Called the Dystrophin-glycoprotein Complmentioning

confidence: 99%

ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D

Ettinger

Feng

Sanes

1997

Journal of Biological Chemistry

154

134

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The sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Mutations in all four known sarcoglycan genes (␣, ␤, ␥, and ␦) have been found in humans with limb-girdle muscular dystrophy. We have identified a novel protein, ⑀-sarcoglycan, that shares 44% amino acid identity with ␣-sarcoglycan (adhalin). We show that ⑀-sarcoglycan is a membrane-associated glycoprotein and document its expression by Northern blotting, immunoblotting, and immunofluorescence. In contrast to ␣-␦ sarcoglycans, which are expressed predominantly or exclusively in striated muscle, ⑀-sarcoglycan is broadly distributed in muscle and nonmuscle cells of both embryos and adults. These results raise the possibility that sarcoglycan-containing complexes mediate membrane-matrix interactions in many cell types.A group of proteins called the dystrophin-glycoprotein complex (DGC) 1 is critical to the stability of muscle fiber membranes (1, 2). Components of the DGC include several cytoplasmic proteins (for example dystrophin and the syntrophins) and two subcomplexes (3) of transmembrane glycoproteins, the dystroglycans (␣ and ␤; Ref. 4), and the sarcoglycans (␣, ␤, ␥, and ␦; Refs. 5-11). The best characterized component of the DGC, dystrophin, is a 427-kDa rod-shaped protein that binds cytoskeletal actin and is associated with the cytoplasmic face of the membrane (12,13). Loss of dystrophin leads to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and cardiac muscle (14). Dystroglycans bind dystrophin intracellularly and laminin extracellularly, thus forming a critical link between the extracellular matrix and the cytoskeleton (15). The sarcoglycans are less well characterized, but three lines of evidence suggest that they may also be involved in membranematrix interactions. First, mutations in all four sarcoglycan genes have been found in patients with limb-girdle muscular dystrophy (6 -8, 10, 16 -21). Second, treatment of cultured muscle cells with antisense oligonucleotides to ␣-sarcoglycan inhibits their adhesion to substrata (22). Third, the laminin isoform composition of muscle fiber basal lamina is altered in patients lacking ␣-sarcoglycan (23, 24). Thus, an attractive hypothesis is that the sarcoglycans and dystroglycans mediate related interactions of muscle cells with basal lamina, both of which are crucial for membrane integrity.Recently, homologues of dystrophin and components of the DGC have been found in numerous nonmuscle tissues. For example, two homologues of dystrophin, utrophin and dystrophin-related protein 2, are expressed at higher levels in some nonmuscle tissues than in muscle (25,26). Moreover, whereas 427-kDa dystrophin is largely confined to muscle, smaller products of the same gene, generated from alternative promoters and by alternative splicing, are widely distributed (12,27). Likewise, cytoplasmic proteins associated with the DGC such as dystrobrevin and the syntrophins and transmembrane compone...

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“…Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by a mutation in the dystrophin gene, located on chromosome Xp21. Dystrophin is associated with a complex of transmembrane glycoproteins, the dystrophin‐glycoprotein complex, and acts as a transsarcolemmal linker between the subsarcolemmal cytoskeleton and the extracellular matrix [1–4]. Loss of this complex results in mechanical instability of the sarcolemma [5], rendering dystrophic muscle more susceptible to stress [6, 7]resulting in an increased activity of ‘leak' [8, 9], and/or stretch‐inactivated Ca 2+ channels [10–13].…”

Section: Introductionmentioning

confidence: 99%

Creatine supplementation improves intracellular Ca²⁺ handling and survival in mdx skeletal muscle cells

et al. 1998

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Dystrophin-glycoprotein complex

Cited by 71 publications

References 48 publications

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D

Creatine supplementation improves intracellular Ca²⁺ handling and survival in mdx skeletal muscle cells

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Dystrophin-glycoprotein complex

Cited by 71 publications

References 48 publications

Convergent regulation of skeletal muscle Ca 2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca 2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

ε-Sarcoglycan, a Broadly Expressed Homologue of the Gene Mutated in Limb-Girdle Muscular Dystrophy 2D

Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells

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Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Convergent regulation of skeletal muscle Ca ²⁺ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Creatine supplementation improves intracellular Ca²⁺ handling and survival in mdx skeletal muscle cells