Shank Proteins Differentially Regulate Synaptic Transmission
Name
ENEURO.0163-15.2017.full.pdf
Description
Published version
Size
1.2 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Shi, Rebecca D.
Redman, Patrick
Ghose, Dipanwita
Hwang, Hongik
Liu, Yan
Ren, Xiaobai
Ding, Lei J.
Liu, Mingna
Jones, Kendrick
Xu, Weifeng
Date Issued
December 2017
Journal
eNeuro
Publisher
Society for Neuroscience
Citation
Shi, Rebecca et al. "Shank Proteins Differentially Regulate Synaptic Transmission." eNeuro 4, 6 (December 2017): ENEURO.0163-15.2017 © 2017 Shi et al
Version
Final published version
Abstract
Shank proteins, one of the principal scaffolds in the postsynaptic density (PSD) of the glutamatergic synapses, have been associated with autism spectrum disorders and neuropsychiatric diseases. However, it is not known whether different Shank family proteins have distinct functions in regulating synaptic transmission, and how they differ from other scaffold proteins in this aspect. Here, we investigate the role of Shanks in regulating glutamatergic synaptic transmission at rat hippocampal SC-CA1 synapses, using lentivirus-mediated knockdown and molecular replacement combined with dual whole-cell patch clamp in hippocampal slice culture. In line with previous findings regarding PSD-MAGUK scaffold manipulation, we found that loss of scaffold proteins via knockdown of Shank1 or Shank2, but not Shank3, led to a reduction of the number but not the unitary response of AMPAR containing synapses. Only when both Shank1 and Shank2 were knocked down, were both the number and the unitary response of active synapses reduced. This reduction was accompanied by a decrease in NMDAR-mediated synaptic response, indicating more profound deficits in synaptic transmission. Molecular replacement with Shank2 and Shank3c rescued the synaptic transmission to the basal level, and the intact sterile _-motif (SAM) of Shank proteins is required for maintaining glutamatergic synaptic transmission. We also found that altered neural activity did not influence the effect of Shank1 or Shank2 knockdown on AMPAR synaptic transmission, in direct contrast to the activity dependence of the effect of PSD-95 knockdown, revealing differential interaction between activity-dependent signaling and scaffold protein families in regulating synaptic AMPAR function. Keywords: ASD; bicuculline; excitatory; hippocampus; mini; Prosap1
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1523/eneuro.0163-15.2017
