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PMID:8607994

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Citation

Gesemann, M, Cavalli, V, Denzer, AJ, Brancaccio, A, Schumacher, B and Ruegg, MA (1996) Alternative splicing of agrin alters its binding to heparin, dystroglycan, and the putative agrin receptor. Neuron 16:755-67

Abstract

Agrin is a heparan sulfate proteoglycan that induces aggregation of acetylcholine receptors (AChRs) at the neuromuscular synapse. This aggregating activity is modulated by alternative splicing. Here, we compared binding of agrin isoforms to heparin, alpha-dystroglycan, and cultured myotubes. We find that the alternatively spliced 4 amino acids insert (KSRK) is required for heparin binding. The binding affinity of agrin isoforms to alpha-dystroglycan correlates neither with binding to heparin nor with their AChR-aggregating activities. Moreover, the minimal fragment sufficient to induce AChR aggregation does not bind to alpha-dystroglycan. Nevertheless, this fragment still binds to cultured muscle cells. Its binding is completed only by agrin isoforms that are active in AChR aggregation, and therefore this binding site is likely to represent the receptor that initiates AChR clustering.

Links

PubMed

Keywords

Agrin/chemistry; Agrin/genetics; Agrin/metabolism; Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Cell Line; Chickens; Cytoskeletal Proteins/metabolism; Dystroglycans; Heparin/metabolism; Membrane Glycoproteins/metabolism; Mice; Molecular Sequence Data; Muscles/metabolism; Receptors, Cholinergic/chemistry; Receptors, Cholinergic/metabolism; Receptors, Growth Factor/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:AGRIN

involved_in

GO:0043113: receptor clustering

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:AGRIN

enables

GO:0002162: dystroglycan binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:AGRIN

enables

GO:0030548: acetylcholine receptor regulator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:AGRIN

enables

GO:0008201: heparin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

See also

References

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