Conclusions

Lateral diffusion of surface neurotransmitter receptors has emerged as a key pathway to regulate receptor trafficking and surface distribution, in addition to their cycling between intracellular and plasma membrane pools. The various diffusion patterns that a receptor display over time indicate that its lateral diffusion is modulated by the receptor environment, such as interactions with other proteins (e.g. scaffold proteins) as well as intracellular (e.g. actin skeleton) and extracellular (e.g. proteoglycan matrix) protein networks. During synaptogenesis, receptors aggregate and cluster within developing synapses. As presented in this chapter, lateral diffusion of receptors is likely to play an important role in such process since receptor lateral diffusion is high during synaptogenesis, providing favourable conditions for receptor trapping within synaptic contact. The "diffusion-trap" model for receptor accumulation in developing synapses, initially established for developing neuromuscular junctions, has then gain experimental supports from excitatory and inhibitory synapses. Direct evidence to test the role of receptor lateral diffusion in synapse maturation is however still lacking due to the absence of adequate tools to precisely control extrasynaptic receptor lateral diffusion. The development of several approaches to tackle this issue will certainly unravel receptor trafficking mechanisms involved in synaptic maturation and plasticity. Within the developing synapse, it also emerges that neurotransmitter release generates instability for AChRs and AMPARs, and their stabilization requires additional factors (e.g. agrin for AChR and NARP for AMPAR) or the accumulation of scaffold proteins. Finally, it has been proposed that receptors of the immune synapses reach the contact zone by undirected lateral diffusion, and interactions with other synaptic proteins are required for their stabilization81. Altogether we propose that the lateral diffusion of plasma membrane proteins represents a common pathway to build intercellular contacts.

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