A membrane skeleton that clusters nicotinic acetylcholine receptors in muscle

We have presented ultrastructural and semiquantitative immunofluorescence evidence to support the idea that AChR are clustered in rat myotubes by virtue of their ability to associate with a spectrin-based membrane skeleton. Many of the interactions postulated to be involved in the formation of this skeleton, and in the anchoring of AChR to it, must still be examined at the biochemical level, but the overall similarity of this structure to that of the human erythrocyte is already clear. The ability of different members of the spectrin superfamily to associate in various combinations to form distinct plasmalemmal domains provides some exciting hints as to how the surface membrane can be organized efficiently to subserve multiple purposes. One of the challenges of future research will be to learn how innervation regulates the assembly of the membrane skeleton at the developing NMJ, and how this structure is altered as the junction matures. Another will be to learn if the principles of neuromuscular synaptogenesis are relevant to interactions between neurons in the brain, where cells must distinguish between multiple synaptic inputs and assemble synaptic structures at thousands of distinct sites on the neurolemma. Members of the spectrin superfamily have been identified in synaptic structures in the central nervous system (e.g., Carlin et al., 1983; LeVine and Sahyoun, 1986; Malchiodi-Albedi et al., 1993), so much of what we have learned at the neuromuscular junction may be applicable to central synapses.