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-Catenin and Acetylcholine Receptor Clustering

It’s a story that has touched the careers of many neuroscientists: the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction. This week, Zhang et al. add -catenin to a list of molecular characters that already includes agrin, rapysn, and MuSK (muscle-specific tyrosine kinase). The authors found -catenin in a two-hybrid screen using rapsyn as bait. They confirmed that the interaction was direct, and that -catenin coprecipitated with AChR complexes in control myotubes, but not in myotubes derived from rapsyn / mice. In a nicely controlled set of experiments, suppression of -catenin by a short hairpin RNA reduced agrin-induced clustering of AChRs in C2C12 myoblasts. Although -catenin is multifunctional, its action here did not involve the Wnt signaling pathway. Rather, an interaction of -catenin with -catenin was required. Thus, the authors suggest that -catenin acts downstream of rapsyn to affect AchR clustering through cytoskeletal linkages.