Localization of dystrophin relative to acetylcholine receptor domains in electric tissue and adult and cultured skeletal muscle.

Sealock, Robert; Butler, Margaret H.; Kramarcy, Neal R.; Gao, Kuixiong; Murnane, Amy A.; Douville, Karen; Froehner, Stanley C.

doi:10.1083/jcb.113.5.1133

Cited by 135 publications

(95 citation statements)

References 66 publications

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“…Normally dystrophin is distributed throughout muscle fibers but is concentrated at the NMJ (Watkins et al, 1988), particularly in synaptic troughs (Byers et al, 1991;Sealock et al, 1991;Bewick et al, 1992) in which the receptor density is low (Fertuck and Salpeter, 1974;Salpeter et al, 1984). Therefore, dystrophin is unlikely to anchor AChRs directly.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Salpeter

1997

J. Neurosci.

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Acetylcholine receptors (AChRs) are present at the top of the postsynaptic membrane of the neuromuscular junction (NMJ) at very high density, possibly anchored to cytoskeletal elements. The present study investigated whether AChR degradation is affected in animals lacking dystrophin, a protein that is an integral part of the cytoskeletal complex and is missing in Duchenne muscular dystrophy. The animal model for Duchenne muscular dystrophy, the mutant mdx mouse, was used to determine whether disruption of the cytoskeleton, caused by the absence of dystrophin, affects AChR degradation. Of the two populations of junctional AChRs, Rs (expressed in innervated adult muscles) and Rr (expressed in embryonic or denervated muscles), only Rs are affected in mdx animals. In innervated mdx soleus, diaphragm, and sternomastoid muscles, the AChRs have an accelerated degradation rate (t 1/2 of ϳ3-5 d), similar to that acquired by Rs in control muscles after denervation. The Rs in mdx NMJs do not accelerate further when the muscles are denervated. The absence of dystrophin does not affect the degradation rate of the Rr AChRs (t 1/2 of 1 d), which are expressed after denervation in mdx as in control muscles. These results suggest that dystrophin or an intact cytoskeletal complex may be required for neuronal stabilization of Rs receptors at the adult neuromuscular junctions.

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Section: Discussionmentioning

confidence: 99%

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Salpeter

1997

J. Neurosci.

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“…mAb 1351 is directed against an epitope within the PDZ domain of syntrophin (S. H. Gee and S. C. Froehner, unpublished data) and recognizes all known mouse syntrophin isoforms (Peters et al, 1994(Peters et al, , 1997. mAb 1808 against dystrophin has been described previously (Sealock et al, 1991). Isoformspecific monoclonal antibodies to K ϩ channel ␣ subunits (Bekele-Arcuri et al, 1996) were a generous gift from Dr. James S. Trimmer (State University of New York at Stony Brook).…”

Section: Methodsmentioning

confidence: 99%

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

et al. 1998

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Syntrophins are cytoplasmic peripheral membrane proteins of the dystrophin-associated protein complex (DAPC). Three syntrophin isoforms, ␣1, ␤1, and ␤2, are encoded by distinct genes. Each contains two pleckstrin homology (PH) domains, a syntrophin-unique (SU) domain, and a PDZ domain. The name PDZ comes from the first three proteins found to contain repeats of this domain (PSD-95, Drosophila discs large protein, and the zona occludens protein 1). PDZ domains in other proteins bind to the C termini of ion channels and neurotransmitter receptors containing the consensus sequence (S/T)XV-COOH and mediate the clustering or synaptic localization of these proteins. Two voltage-gated sodium channels (NaChs), SkM1 and SkM2, of skeletal and cardiac muscle, respectively, have this consensus sequence. Because NaChs are sarcolemmal components like syntrophins, we have investigated possible interactions between these proteins. NaChs copurify with syntrophin and dystrophin from extracts of skeletal and cardiac muscle. Peptides corresponding to the C-terminal 10 amino acids of SkM1 and SkM2 are sufficient to bind detergentsolubilized muscle syntrophins, to inhibit the binding of native NaChs to syntrophin PDZ domain fusion proteins, and to bind specifically to PDZ domains from ␣1-, ␤1-, and ␤2-syntrophin. These peptides also inhibit binding of the syntrophin PDZ domain to the PDZ domain of neuronal nitric oxide synthase, an interaction that is not mediated by C-terminal sequences. Brain NaChs, which lack the (S/T)XV consensus sequence, also copurify with syntrophin and dystrophin, an interaction that does not appear to be mediated by the PDZ domain of syntrophin. Collectively, our data suggest that syntrophins link NaChs to the actin cytoskeleton and the extracellular matrix via dystrophin and the DAPC.

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“…Production and characterization of the antisyntrophin mAb 1351 and antidystrophin mAb 1958 have been described previously [15,21]. Lithium diiodosalycilate (LIS) was purchased from Eastman Kodak (Rochester, NY).…”

Section: Methodsmentioning

confidence: 99%

Direct binding of Torpedo syntrophin to dystrophin and the 87 kDa dystrophin homologue

Dwyer

Froehner

1995

FEBS Letters

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Syntrophin, a 58-kDa membrane-associated protein, is one component of a protein complex associated with dystrophin and other members of the dystrophin family, including the 87-kDa homologue (87K protein). To characterize interactions between syntrophin and 87K protein, we used an in vitro overlay binding assay. We demonstrate that purified Torpedo syntrophin binds directly to dystrophin and 871(. By expressing overlapping regions of the 87K protein as bacterial fusion proteins for binding targets, we show that a 52-amino acid region of 87K (residues 375-426) is sufficient for binding syntrophin.Key words: Syntrophin; Dystrophin; Binding site; Torpedo into two groups based on isoelectric point: acidic (~, pI = 6.7) or basic (ill and f12, pI = 9 +) [19]. In skeletal muscle, c~-syntrophin is found on the sarcolemm a, in a distribution like that of dystrophin and the 87K protein, while fl2-syntrophin is localized to the neuromuscular junction [20].Here, we characterize the binding of Torpedo syntrophin to dystrophin and 87K. Using an in vitro blot overlay assay, we show that Torpedo syntrophin (an ~-syntrophin) binds directly to dystrophin and 87K. Using fusion proteins encoding portions of 87K, we map a binding site of syntrophin to residues 375-426.

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Localization of dystrophin relative to acetylcholine receptor domains in electric tissue and adult and cultured skeletal muscle.

Cited by 135 publications

References 66 publications

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

Direct binding of Torpedo syntrophin to dystrophin and the 87 kDa dystrophin homologue

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