The submembrane machinery for nicotinic acetylcholine receptor clustering.

Abstract

HE segregation of membrane proteins into specialized domains is important for many aspects of cell function, especially those involving cell-cell interaction and conununication. Of particular interest to cellular and molecular neurobiologists are the highly specialized distributions of ion channels at synapses. Both the pre- and postsynaptic membranes exhibit organized arrays ofion channels that are important for synaptic transmission. At the neuromuscularjunction, voltage-activated calcium channels are clustered at presynaptic active zones the sites ofacetylcholine release. Directly across the synaptic gap from active zones are regions of the postsynaptic membrane containing extraordinarily high concentrations nicotinic acetylcholine receptors A few mi-crons away from the the concentration of receptors abruptly decreases to very low levels. >90% of the AChR in a skeletal muscle fiber are found at the synapse, an area that occupies <0.1% of the total muscle membrane. The AM is a pentameric complex of four different trans-membrane subunits that is inherently capable of diffusion within theplane ofthe membrane. Understanding the molecular mechanisms responsible for anchoring AChR at postsynaptic sites has been a major issue for researchers in-terested in neuromuscular synaptogenesis.