Molecular interactions between pre- and postsynaptic membranes play critical roles during the development, function and maintenance of synapses. Synaptic interactions are mediated by cell surface receptors that may be held in place by trans-synaptic adhesion or intracellular binding to membrane-associated scaffolding and signaling complexes. Despite their role in stabilizing synaptic contacts, synaptic adhesion molecules undergo turnover and degradation during all stages of a neuron’s life. Here we review current knowledge about membrane trafficking mechanisms that regulate turnover of synaptic adhesion molecules and the functional significance of turnover for synapse development and function. Based on recent proteomics, genetics and imaging studies, synaptic adhesion molecules exhibit remarkably high turnover rates compared to other synaptic proteins. Degradation occurs predominantly via endolysosomal mechanisms, with little evidence for roles of proteasomal or autophagic degradation. Basal turnover occurs both during synaptic development and maintenance. Neuronal activity typically stabilizes synaptic adhesion molecules while downregulating neurotransmitter receptors based on turnover. In conclusion, constitutive turnover of synaptic adhesion molecules is not a necessarily destabilizing factor, but a basis for the dynamic regulation of trans-synaptic interactions during synapse formation and maintenance.
Posted inNews Publications
Review Article on Turnover of Synaptic Adhesion molecules
