Identification and purification of an agrin receptor from torpedo postsynaptic membranes: A heteromeric complex related to the dystroglycans

Bowe, Mark A.; Deyst, Katherine A.; Leszyk, John D.; Fallon, Justin R.

doi:10.1016/0896-6273(94)90324-7

Cited by 295 publications

(236 citation statements)

References 45 publications

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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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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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“…The clones were then combined to minimize regions of overlap and maximize the region of hybridization to the chromosomes. In situ hybridization with the three genomic clones confirmed adhalin's map position as chromosome 17 and delineated further its location at 17q21 (Fig. 5).…”

Section: Analysis By Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 83%

“…Together these observations have identified one potential role of the dystrophin-glycoprotein complex as a bridge between the cytoskeleton, sarcolemma, and extracellular matrix. Recently, a second role for the DAPs, specifically dystroglycan, was identified when it was shown that the receptor for agrin, a protein implicated in acetylcholine receptor localization, is dystroglycan (17)(18)(19). Adhalin, the 50-kDa DAP, was also found specifically at the sites of receptor clustering (18).…”

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confidence: 98%

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Human adhalin is alternatively spliced and the gene is located on chromosome 17q21.

McNally

Yoshida

Mizuno

et al. 1994

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

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Mutations in the dystrophin gene cause the X chromosome-linked, recessive Duchenne and Becker muscular dystrophies. Dystrophin, a large cytoskeletal protein, copurifles with a complex of dystrophin-aclated proteins which serve to anchor dystrophin to the sarcolemma. One of these associated proteins, adhalin, has been implicated as a candidate for severe childhood autosomal recessive muscular dystrophy (SCARMD) due to absence of anti-adhalin sning in muscle biopsy samples taken from SCARMD patients. Furthermore, the Duchenne-like dystrophic phenotype seen in the SCARMD families was shown to be tightly linked to chromosome 13 markers. To determine the genetic mutation responsible for autosomal dystrophy, we characterized the human adhalin gene. Contrary to our expectation, human adhalin was mapped to chromosome 17q21, excluding adhalin as the gene causing chromosome 13-associated SCARMD. Additionaily, a splice form of adhalin message was found that predicts a 35-kDa nontransmembrane adhalin. The expression of both adhalin splice forms is exclusively restricted to striated muscle, unlike other components of the dystrophin-glycoprotein complex.Genetic analyses of patients with Duchenne and Becker muscular dystrophy (DMD/BMD) have demonstrated a correlation between mutations in dystrophin's carboxyl terminus and a more severe clinical course (1). The carboxyl terminus of dystrophin binds a complex of dystrophinassociated proteins (DAPs), and components of this glycoprotein complex are decreased in DMD (2-5). Several DAPs have been identified by virtue of their copurification with dystrophin (6-8). These include the 156-and 43-kDa glycoproteins, together named dystroglycan, that are produced from one transcript encoded by a single gene on chromosome 3p21 (9,10). Three separate genes encode the 59-kDa nonglycosylated members of the complex, called syntrophins (11,12). Three additional proteins (50, 35, and 25 kDa) also participate in dystrophin's membrane interaction (6-8, 13). Using partial peptide sequences generated from proteolytic digestion of the rabbit 50-kDa DAP, Roberds et al. (13) identified a cDNA encoding the rabbit 50-kDa DAP and termed it adhalin. Isoelectric focusing analysis of the smaller components of the glycoprotein complex has suggested that the 35-kDa DAP may be heterogeneous (8).Dystroglycan and the syntrophins are expressed in tissues that lack the full-length dystrophin (10)(11)(12). This has raised speculation that in vivo, dystroglycan and the syntrophins may interact with proteins other than dystrophin. In vitro, syntrophin binds the carboxyl terminus of dystrophin, and dystroglycan has been shown to bind the extracellular matrix component laminin in a gel overlay assay (9,(14)(15)(16) gene (20, 24).In an effort to understand the genetic mutation responsible for SCARMD, we isolated and characterized cDNA and genomic sequences encoding human adhalin. To our surprise, the adhalin gene resides on chromosome 17q21, unlinked to the chromosome 13-encoded SCARMD locus. Additionally, a spli...

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“…According to recent studies [24][25][26][27], dystroglycan localized with utrophin in this structure could be an agrin receptor and would thus play a key role in synapse formation via acetyl choline receptor clustering. Torpedo electrocytes were the first tissues in which interactions between agrin and dystroglycan were tentatively identified [28]. The electric organ and its innervation with electrocyte nerves provide a giant model for neuromuscular junction formation and exchanges between peripheral motor nerves and their effectors.…”

Section: Introductionmentioning

confidence: 99%

Presence of long and short dystrophin and/or utrophin products in Torpedo marmorata peripheral nerves

et al. 1996

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Peripheral nerves from rabbit and Torpedo marmorata were comparatively analyzed for the presence of short dystrophin products. Western blot analyses of Torpedo marmorata peripheral nerve extracts revealed the existence of three proteins belonging to the dystrophin family: a M, 400 kDa protein band detected with dystrophin/utrophin, dystrophin-specific and Torpedo utrophin-specific antibodies, a molecule identified as Dpll6 and, for the frst time at the protein level, a new protein probably corresponding to Upll6. All of these products were carefully identified according to the specificities of the monoclonal antibodies used. In immunofluorescence studies, clear staining of the thin rim surrounding each Schwann cell-axon unit was observed in both Torpedo marmorata and rabbit peripheral nerves, showing colocalization of all of these molecules. Their potential functions were discussed in comparison to similar products found in rabbit peripheral nerves.

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Identification and purification of an agrin receptor from torpedo postsynaptic membranes: A heteromeric complex related to the dystroglycans

Cited by 295 publications

References 45 publications

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Human adhalin is alternatively spliced and the gene is located on chromosome 17q21.

Presence of long and short dystrophin and/or utrophin products in Torpedo marmorata peripheral nerves

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