Identification of an elaborate complex mediating postsynaptic inhibition.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Uezu, A; Kanak, DJ; Bradshaw, TWA; Soderblom, EJ; Catavero, CM; Burette, AC; Weinberg, RJ; Soderling, SH

Published Date

  • September 9, 2016

Published In

Volume / Issue

  • 353 / 6304

Start / End Page

  • 1123 - 1129

PubMed ID

  • 27609886

Pubmed Central ID

  • PMC5432043

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aag0821


  • eng

Conference Location

  • United States