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Cell DOI:10.1016/j.cell.2016.07.041

Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts.

Publication TypeJournal Article
Year of Publication2016
AuthorsLoh, KH, Stawski, PS, Draycott, AS, Udeshi, ND, Lehrman, EK, Wilton, DK, Svinkina, T, Deerinck, TJ, Ellisman, MH, Stevens, B, Carr, SA, Ting, AY
Date Published2016 Aug 25
KeywordsAnimals, Antigens, CD, Cell Adhesion Molecules, Neuronal, GABAergic Neurons, Glutamic Acid, HEK293 Cells, Humans, Immunoglobulins, Membrane Glycoproteins, Mice, Nerve Tissue Proteins, Neural Cell Adhesion Molecules, Peroxidase, Proteome, Proteomics, Rats, Receptors, GABA, Recombinant Fusion Proteins, Synaptic Membranes, Thalamus

Cellular compartments that cannot be biochemically isolated are challenging to characterize. Here we demonstrate the proteomic characterization of the synaptic clefts that exist at both excitatory and inhibitory synapses. Normal brain function relies on the careful balance of these opposing neural connections, and understanding how this balance is achieved relies on knowledge of their protein compositions. Using a spatially restricted enzymatic tagging strategy, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons. These proteomes reveal dozens of 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 potential specificity factor influencing Neuroligin-2's recruitment of presynaptic neurotransmitters at inhibitory synapses.


Alternate JournalCell
PubMed ID27565350
PubMed Central IDPMC5167540
Grant ListR01 CA186568 / / / International
P41 GM103412 / GM / NIGMS NIH HHS / United States
P41GM103412 / / / International
R01 CA186568 / CA / NCI NIH HHS / United States
R01 NS092578 / / / International
R01GM086197 / / / International
R01 NS071008 01A1 / / / International
R01 NS071008 / NS / NINDS NIH HHS / United States
/ HHMI / HHMI / United States
R01 NS092578 / NS / NINDS NIH HHS / United States
R01 GM086197 / GM / NIGMS NIH HHS / United States