Cooperation between the products of different nuclei in hybrid myotubes produces localized acetylcholine receptor clusters

Cultured myotubes form clusters of acetylcholine receptors (AChRs) spontaneously and at sites of nerve-muscle contact. To investigate the cellular mechanisms by which spontaneous clusters are formed, we have made hybrid myotubes between a mouse muscle cell variant, S27, that does not cluster AChRs, and one that does not make AChRs. We have also made hybrid myotubes using S27 and quail muscle cells. In both cases, clusters of AChRs were found near the non-S27 nuclei; in the case of the interspecific hybrids, mouse AChRs were associated with extracellular matrix components contributed by the quail nuclei. Our results suggest that AChRs made by one nucleus can be clustered by localized extracellular matrix produced by a different nucleus and provide an example of nuclear cooperation between the products of different nuclei within multinucleated muscle fibers.