A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency
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.
Additional Information
© 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. Received: 11 October 2019; Accepted: 14 January 2020; Published: 15 January 2020. This work was supported by U. S. National Institute of Mental Health Grant MH115456 to MBK, the Allen and Lenabelle Davis Foundation (MBK), U.S. National Science Foundation Fellowship 1612289 to TLM, the Department of Biotechnology, India (SC and PCK), Simons Foundation Autism Research Initiative Grant 529085 to PK, Patrick Wild Centre (SMT and PCK), and Medical Reasearch Council UK Grant MR/P006213/1 to SMT and PCK. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author contributions: Tara L Mastro, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation; Anthony Preza, Data curation, Investigation, Writing - review and editing; Shinjini Basu, Resources, Investigation; Sumantra Chattarji, Peter C Kind, Resources, Funding acquisition; Sally M Till, Resources, Investigation, Visualization; Mary B Kennedy, Resources, Formal analysis, Supervision, Funding acquisition, Validation, Visualization, Project administration. 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. Data availability: All data generated or analysed during this study are included in the manuscript and supporting files.Attached Files
Published - elife-52656-v2.pdf
Supplemental Material - elife-52656-supp1-v2.pdf
Supplemental Material - elife-52656-transrepform-v2.pdf
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Additional details
- PMCID
- PMC6994236
- Eprint ID
- 100838
- DOI
- 10.7554/elife.52656
- Resolver ID
- CaltechAUTHORS:20200122-112342378
- MH115456
- NIH
- Allen and Lenabelle Davis Foundation
- DBI-1612289
- NSF
- Department of Biotechnology (India)
- 529085
- Simons Foundation
- Patrick Wild Centre
- MR/P006213/1
- Medical Research Council (UK)
- Created
-
2020-01-22Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering