ORGANIZING EFFECTS OF RAPSYN ON NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS

Targeting receptors to appropriate locations on the cell surface is a critical task for neurons. We have examined the possibility that rapsy n controls the distribution of nicotinic receptors on neurons as it do es nicotinic receptors on muscle fibers. Cotransfection of QT6 cells w ith rapsyn and neuronal nicotinic receptor cDNA constructs produced re ceptor aggregates or clusters that codistributed in part with rapsyn p rotein. Though all nicotinic receptor subtypes tested were affected by rapsyn, receptors containing the alpha 7 gene product were among the most responsive. In addition, rapsyn caused a portion of the nicotinic receptors containing alpha 7 subunits to become resistant to solubili zation with nonionic detergent and to display a marked increase in met abolic stability. The results are consistent with rapsyn linking the r eceptors to cyloskeletal elements and suggest that it may play an orga nising role determining the fate and location of nicotinic receptors o n neurons.