Significant progress has been made toward the elucidation of the molecular mechanisms underlying the biogenesis and stabilization of postsynaptic membrane specializations at the neuromuscular junction of vertebrate skeletal muscle. The emerging picture reveals a continuous molecular link from the extracellular matrix within the synaptic cleft via integral and peripheral membrane proteins to the subsarcolemmal cytoskeleton. The formation and maintenance of synaptic contacts between neurons in the CNS might follow similar architectural principles but involve different molecules. The biogenesis of glycinergic postsynaptic membrane specializations depends on the widely expressed peripheral membrane protein gephyrin, which anchors the neurotransmitter receptor to underlying cytoskeletal elements in a dynamic manner. This anchoring mechanism could also contribute to the plasticity of glycinergic synapses. Other types of neurotransmitter receptors, like GABAA- and glutamate receptors, may have evolved different molecular mechanisms to ensure their localization in postsynaptic membrane specializations. The Neuroscientist 2:100-108, 1996
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