2. Academic Validation
  3. Identification of an elaborate complex mediating postsynaptic inhibition

Identification of an elaborate complex mediating postsynaptic inhibition

  • Science. 2016 Sep 9;353(6304):1123-9. doi: 10.1126/science.aag0821.
Akiyoshi Uezu 1,  Daniel J Kanak 1,  Tyler W A Bradshaw 1,  Erik J Soderblom 2,  Christina M Catavero 1,  Alain C Burette 3,  Richard J Weinberg 3,  Scott H Soderling 4
Affiliations

Affiliations

  • 1 The Department of Cell Biology, Duke University Medical School, Durham, NC 27703, USA.
  • 2 The Department of Cell Biology, Duke University Medical School, Durham, NC 27703, USA. Duke Proteomics and Metabolomics Shared Resource and Duke Center for Genomic and Computational Biology, Duke University Medical School, Durham, NC 27703, USA.
  • 3 Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA. Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
  • 4 The Department of Cell Biology, Duke University Medical School, Durham, NC 27703, USA. The Department of Neurobiology, Duke University Medical School, Durham, NC 27703, USA. [email protected].
PMID: 27609886 DOI: 10.1126/science.aag0821
Abstract

Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins. Quantitative mass spectrometry not only recapitulated known inhibitory postsynaptic proteins but also revealed a large network of new proteins, many of which are either implicated in neurodevelopmental disorders or are of unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion of one of these previously uncharacterized proteins, InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of miniature inhibitory currents, and increased excitability in the hippocampus. Our findings uncover a rich and functionally diverse assemblage of previously unknown proteins that regulate postsynaptic inhibition and might contribute to developmental brain disorders.

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