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Cell. 2016 Aug 25;166(5):1295-1307.e21. doi: 10.1016/j.cell.2016.07.041.

Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts.

Author information

1
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
2
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3
F.M. Kirby Neurobiology Center, Boston Children's Hospital (BCH) and Harvard Medical School (HMS), Boston, MA 02115, USA.
4
National Center for Microscopy and Imaging Research, University of California at San Diego, La Jolla, CA 92093 USA; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
5
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: ayting@stanford.edu.

Abstract

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.

PMID:
27565350
PMCID:
PMC5167540
DOI:
10.1016/j.cell.2016.07.041
[Indexed for MEDLINE]
Free PMC Article

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