AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding domain for alpha-dystroglycan

被引:37
作者
Meier, T
Gesemann, M
Cavalli, V
Ruegg, MA
Wallace, BG
机构
[1] UNIV COLORADO,HLTH SCI CTR,DEPT PHYSIOL,DENVER,CO 80262
[2] UNIV BASEL,BIOZENTRUM,DEPT PHARMACOL,BASEL,SWITZERLAND
关键词
acetylcholine receptor; agrin; dystroglycan; neuromuscular junction; protein tyrosine phosphorylation;
D O I
10.1002/j.1460-2075.1996.tb00622.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Agrin induces both phosphorylation and aggregation of nicotinic acetylcholine receptors (AChRs) when added to myotubes in culture, apparently by binding to a specific receptor on the myotube surface. One such agrin receptor is alpha-dystroglycan, although binding to alpha-dystroglycan appears not to mediate AChR aggregation. To determine whether agrin-induced AChR phosphorylation is mediated by alpha-dystroglycan or by a different agrin receptor, fragments of recombinant agrin that differ in affinity for alpha-dystroglycan were examined for their ability to induce AChR phosphorylation and aggregation in mouse C2 myotubes. The carboxy-terminal 95 kDa agrin fragment agrin-c95(A0B0), which binds to alpha-dystroglycan with high affinity, failed to induce AChR phosphorylation and aggregation. In contrast, agrin-c95(A4B8), which binds less strongly to alpha-dystroglycan, induced both phosphorylation and aggregation, as did a small 21 kDa fragment of agrin, agrin-c21(B8), that completely lacks the binding domain for alpha-dystroglycan. We conclude that agrin-induced AChR phosphorylation and aggregation are triggered by an agrin receptor that is distinct from alpha-dystroglycan.
引用
收藏
页码:2625 / 2631
页数:7
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