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Proteomic maps of excitatory and inhibitory synaptic clefts revealed by proximity biotinylation

ABSTRACT: Loh KH, Stawski PS, Draycott AS, Udeshi ND, Lehrman EK, Wilton DK, Svinkina T, Deerinck TJ, Ellisman MH, Stevens B, Carr SA, Ting AY. Cell 2016 Excitatory synapses are connections between neurons that promote the propagation of action potentials while inhibitory synapses repress them. Normal brain function relies on the careful balance of these antagonistic connections, which occur via molecularly distinct synaptic clefts. Understanding how this is achieved relies on knowledge of their protein compositions, yet the clefts remain uncharacterized because they cannot be isolated biochemically. Here, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons, using a spatially restricted enzymatic tagging strategy. These proteomes reveal dozens of novel synaptic candidates, and assign numerous known synaptic proteins to a specific cleft type. The molecular differentiation of each cleft allowed us to identify Mdga2 as a specificity factor regulating the presynaptic neurotransmitter recruiting activity of Neuroligin-2 at inhibitory synapses.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (ncbitaxon:10116)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000079849 | MassIVE | Thu Jun 23 08:53:00 BST 2016

REPOSITORIES: MassIVE

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