Dystroglycan binds nerve and muscle agrin

Sugiyama, Janice E.; Bowen, David C.; Hall, Zach W.

doi:10.1016/0896-6273(94)90462-6

Cited by 255 publications

(252 citation statements)

References 62 publications

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“…␤-Dystroglycan is a component of the dystrophin-glycoprotein complex, serving as a transmembrane link between the extracellular peripheral membrane protein ␣-dystroglycan and cytoskeletal dystrophin or utrophin (Ibraghimov-Beskrovnaya et al, 1992). Recently, ␣-dystroglycan was identified as a cell surface binding site for agrin (Bowe et al, 1994;Campanelli et al, 1994;Gee et al, 1994;Sugiyama et al, 1994). This finding has focused much attention on the possible role of the dystrophin-protein complex in mediating the AChR clustering effects of agrin.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

Colledge

Froehner

1997

J. Neurosci.

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Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) is associated with an altered rate of receptor desensitization and also may play a role in agrin-induced receptor clustering. We have demonstrated a previously unsuspected interaction between Torpedo AChR and the adaptor protein Grb2. The binding is mediated by the Src homology 2 (SH2) domain of Grb2 and the tyrosine-phosphorylated ␦ subunit of the AChR. Dephosphorylation of the ␦ subunit abolishes Grb2 binding. A cytoplasmic domain of the ␦ subunit contains a binding motif (pYXNX) for the SH2 domain of Grb2. Indeed, a phosphopeptide corresponding to this region of the ␦ subunit binds to Grb2 SH2 fusion proteins with relatively high affinity, whereas a peptide lacking phosphorylation on tyrosine exhibits no binding. Grb2 is colocalized with the AChR on the innervated face of Torpedo electrocytes. Furthermore, Grb2 specifically copurifies with AChR solubilized from postsynaptic membranes. These data suggest a novel role for tyrosine phosphorylation of the AChR in the initiation of a Grb2-mediated signaling cascade at the postsynaptic membrane.

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Section: Discussionmentioning

confidence: 99%

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

Colledge

Froehner

1997

J. Neurosci.

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“…We have shown previously that AChE activity is tightly colocalized with agrin-induced ectopic AChR clusters (Jones et al, 1997). Full-length cAgrin 7A4B8 binds to laminin-␤2 (Denzer et al, 1997) and to ␣-dystroglycan (Bowe et al, 1994;C ampanelli et al, 1994;Gee et al, 1994;Sugiyama et al, 1994;Gesemann et al, 1996). We therefore asked whether cAgrin 7A4B8 would induce accumulation of laminin-␤2 or dystroglycans at ectopic AChR aggregates.…”

Section: Ectopic Agrin Induces Accumulation Of Several Synaptic Proteinsmentioning

confidence: 99%

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Meier¹,

et al. 1997

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Neural agrin, in the absence of a nerve terminal, can induce the activity-resistant expression of acetylcholine receptor (AChR) subunit genes and the clustering of synapse-specific adult-type AChR channels in nonsynaptic regions of adult skeletal muscle fibers. Here we show that, when expression plasmids for neural agrin are injected into the extrasynaptic region of innervated muscle fibers, the following components of the postsynaptic apparatus are aggregated and colocalized with ectopic agrininduced AChR clusters: laminin-␤2, MuSK, phosphotyrosinecontaining proteins, ␤-dystroglycan, utrophin, and rapsyn. These components have been implicated to play a role in the differentiation of neuromuscular junctions. Furthermore, ErbB2 and ErbB3, which are thought to be involved in the regulation of neurally induced AChR subunit gene expression, were colocalized with agrin-induced AChR aggregates at ectopic nerve-free sites. The postsynaptic muscle membrane also contained a high concentration of voltage-gated Na ϩ channels as well as deep, basal lamina-containing invaginations comparable to the secondary synaptic folds of normal endplates. The ability to induce AChR aggregation in vivo was not observed in experiments with a muscle-specific agrin isoform. Thus, a motor neuron-specific agrin isoform is sufficient to induce a full ectopic postsynaptic apparatus in muscle fibers kept electrically active at their original endplate sites.

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“…1994;Gee et a/. 1994;Bowe et al 1994;Sugiyama et al 1994;Campanelli et al 1996). a-DG is a component of a transmembrane protein complex; dystrophin associated glycoprotein complex (DGC).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively a-DG may activate another receptor either by concentrating or perhaps transferring agrin to this presumed receptor (Sugiyama et al 1994). O r there is a third possibility; motor neurone secretes inactive agrin isoform (agrin 0) as well as active isoform (agrin 8).…”

Section: Mechanism Of Agrin-induced Achr Cluster Formationmentioning

confidence: 99%

Inhibition of agrin‐mediated acetylcholine receptor clustering by utrophin C‐terminal peptides

1996

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Background: Agrin is an extracellular matrix protein that is required for neuromuscular synaptogenesis and is particularly important in the clustering of acetylcholine receptors at post-synaptic sites. Little is known about the signal transduction pathway of agrin-mediated receptor clustering, although cytoskeletal elements and a dystrophin associated glycoprotein complex (DGC) have been implicated. Because agrin binds to a-dystroglycan, a member of the DGC, and the DGC is linked to actin through utrophin at postsynaptic sites, it has been suggested that binding of utrophin to the DGC plays a central role in agrin mediated receptor clustering.

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Dystroglycan binds nerve and muscle agrin

Cited by 255 publications

References 62 publications

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Inhibition of agrin‐mediated acetylcholine receptor clustering by utrophin C‐terminal peptides

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