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
Language
- eng
Conference Location
- United States