A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency
- California Institute of Technology, United States
- University of Edinburgh, United Kingdom
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Abstract
SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walkup et al., 2016). For example, the ratio to PSD-95 of Transmembrane AMPA-Receptor-associated Proteins (TARPs), which mediate binding of AMPA-type glutamate receptors to PSD-95, was increased in young Syngap1+/- mice. Here we show that only females and not males show a highly significant correlation between an increase in TARP and a decrease in synGAP in the PSDs of Syngap1+/- rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Sumantra Chattarji
Funding
National Institute of Mental Health (MH15456)
- Tara L Mastro
- Anthony Preza
- Mary B Kennedy
Allen and Lenabelle Davis Foundation (Professorship)
- Mary B Kennedy
National Science Foundation (Postdoctoral Fellowship)
- Tara L Mastro
Department of Biotechnology , Ministry of Science and Technology
- Sumantra Chattarji
- Peter C Kind
Simons Foundation (Grant 529085)
- Peter C Kind
Patrick Wild Centre (Patrick Wild Centre)
- Sally M Till
- Peter C Kind
Medical Research Council (MR/P006213/1)
- Sally M Till
- Peter C Kind
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (1034-18) of California Institute of Technology.
Reviewing Editor
- Leslie C Griffith, Brandeis University, United States
Publication history
- Received: October 11, 2019
- Accepted: January 14, 2020
- Accepted Manuscript published: January 15, 2020 (version 1)
- Version of Record published: January 31, 2020 (version 2)
Copyright
© 2020, Mastro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency
eLife 9:e52656.
https://doi.org/10.7554/eLife.52656
