Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model

Recent studies indicate an important role of cytoskeleton-associated and lipid-anchored proteins in the formation of inhibitory postsynaptic membrane specializations. Membrane apposition of the tubulin-binding protein gephyrin is essential for the recruitment of inhibitory glycine receptors and GABAA receptors to developing postsynaptic sites. Newly disclosed interactions between gephyrin, exchange factors for G proteins of the Rho and Rac families, the translational regulator RAFT1, and actin-binding proteins like profilin might integrate activity-dependent and trophic-factor-mediated signals at developing postsynaptic sites. A model of inhibitory neurotransmitter receptor clustering, is proposed, in which this process is initiated by receptor-driven activation of phosphatidylinositol 3-kinase.