TY - JOUR
T1 - Alternative splicing of agrin alters its binding to heparin, dystroglycan, and the putative agrin receptor
AU - Gesemann, Matthias
AU - Cavalli, Valeria
AU - Denzer, Alain J.
AU - Brancaccio, Andrea
AU - Schumacher, Beat
AU - Ruegg, Markus A.
N1 - Funding Information:
We thank R. Kammerer for helping to set up the expression system in E. coli. We are grateful to Dr. W. B. Adams for many helpful suggestions during the course of this work and to R. Brandenberger and Drs. G. Jones, T. Meier, B. G. Wallace, and M. J. Werle for reading the manuscript. This work was supported by the Swiss National Science Foundation number 31-33697.92 and the Schweizerische Stiftung für die Erforschung der Muskelkrankheiten.
PY - 1996/4
Y1 - 1996/4
N2 - 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, α-dystroglycan, and cultured myotubes. We find that the alternatively spliced 4 amino acid insert (KSRK) is required for heparin binding. The binding affinity of agrin isoforms to α- 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 α-dystroglycan. Nevertheless, this fragment still binds to cultured muscle cells. Its binding is competed 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.
AB - 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, α-dystroglycan, and cultured myotubes. We find that the alternatively spliced 4 amino acid insert (KSRK) is required for heparin binding. The binding affinity of agrin isoforms to α- 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 α-dystroglycan. Nevertheless, this fragment still binds to cultured muscle cells. Its binding is competed 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.
UR - http://www.scopus.com/inward/record.url?scp=0029958839&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80096-3
DO - 10.1016/S0896-6273(00)80096-3
M3 - Article
C2 - 8607994
AN - SCOPUS:0029958839
SN - 0896-6273
VL - 16
SP - 755
EP - 767
JO - Neuron
JF - Neuron
IS - 4
ER -