Metabolic stabilization of muscle nicotinic acetylcholine receptor by rapsyn

Although the metabolic half-life of muscle endplate acetylcholine receptor (AChR) changes during development and after denervation in the adult, littl e is known about the molecular mechanisms that influence receptor stability . We have investigated the effect on AChR turnover of its interaction with rapsyn, a 43 kDa peripheral membrane protein that is closely associated wit h the AChR in muscle cells and is required for its clustering at endplates. Both in transfected COS cells and in cultured myotubes from rapsyn-negativ e and rapsyn-positive mice, we have found that the presence of rapsyn slows the turnover of AChRs by as much as twofold. The effect was similar for bo th embryonic (alpha(2)beta delta gamma) and adult (alpha(2)beta delta epsil on) AChRs and for AChRs whose beta subunit lacked a putative tyrosine phosp horylation site. Neither colchicine nor cytochalasin D altered AChR turnove r or prevented the rapsyn effect. Mutant rapsyn proteins whose N-terminal m yristoylation signal was eliminated, or whose C terminus or zinc-finger dom ains were deleted, failed to change the rate of receptor turnover. Each of these mutations affects the association of the AChR with rapsyn, suggesting that AChR stability is altered by interaction between the two proteins. Ou r results suggest that, in addition to its role in AChR clustering, rapsyn also functions to metabolically stabilize the AChR.