Journal Article

The role of receptor diffusion in the organization of the postsynaptic membrane

Choquet, Daniel, Triller, Antoine

2003

Overview

Key Points The structure of the postsynaptic membrane is highly heterogeneous and dynamic. Receptors are stabilized by a network that consists of scaffold proteins, adhesion proteins and the cytoskeleton, and changes in the receptor profile of the membrane are mediated by endocytosis, exocytosis and diffusion. Receptor diffusion has a role during the formation of new synapses, and during synaptic turnover and synaptic plasticity. There are five main categories of diffusion, ranging from 'free' to 'confined'. The subsynaptic scaffold network constitutes a barrier to receptor movement, resulting in confined diffusion. Techniques such as single particle tracking and fluorescence recovery after photobleaching have been used to follow receptor movements. Fast random movements are interspersed with periods of relative immobility, indicating the presence of transient submicrometre domains in the membrane that are separated by barriers. Within these domains, receptor diffusion is as fast as expected from theoretical calculations. Receptors can escape these 'corrals' by 'jumping the fence' or by passing through gaps when the membrane skeleton is transiently dissociated. Receptors can diffuse individually or as part of a cluster. Clusters are aggregations of receptors that are stabilized by their associations with scaffold components. Diffusion of cluster-associated receptors may be due to movement of the entire cluster or movement of the individual receptor within the cluster. Equilibrium between receptors entering and exiting subdomains (corrals) accounts for the apparent stability of the postsynaptic membrane. So, gross changes in receptor number during synaptogenesis and synaptic plasticity can be considered to result from a change in the set-point of this equilibrium. Neurotransmitter receptor movement into and out of synapses is one of the core mechanisms for rapidly changing the number of functional receptors during synaptic plasticity. Recent data have shown that rapid gain and loss of receptors from synaptic sites are accounted for by endocytosis and exocytosis, as well as by lateral diffusion of receptors in the plane of the membrane. These events are interdependent and are regulated by neuronal activity and interactions with scaffolding proteins. Here we focus on the physical laws that govern receptor diffusion and stabilization, and how this might reshape how we think about the specific regulation of receptor accumulation at synapses.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological and medical sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Central nervous system / Central Nervous System - physiology / Central neurotransmission. Neuromudulation. Pathways and receptors / Diffusion / Fundamental and applied biological sciences. Psychology / Humans / Kinases / Neurobiology / Neuronal Plasticity - physiology / Neurosciences / Proteins / Receptors, Neurotransmitter - physiology / review-article / Synaptic Membranes - physiology / Synaptic Transmission - physiology / Vertebrates: nervous system and sense organs