A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency.

Mastro, Tara L; Preza, Anthony; Basu, Shinjini; Chattarji, Sumantra; Till, Sally M; Kind, Peter C; Kennedy, Mary B · Elife · 2020

basic_science · Level V

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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 <i>Syngap1</i> 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 <i>Syngap1<sup>+/-</sup></i>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 <i>Syngap1<sup>+/-</sup></i>rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency.

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