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

• Published in: eLife Vol. 9
• Main Authors: Mastro, Tara L, Preza, Anthony, Basu, Shinjini, Chattarji, Sumantra, Till, Sally M, Kind, Peter C, Kennedy, Mary B
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 15.01.2020; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Biochemistry and Chemical Biology; CRISPR; CRISPR-Cas Systems; Datasets; Female; Females; Glutamate; glutamate receptor; Glutamic acid receptors; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Haploinsufficiency; Kinases; Male; Males; Mice; Mice, Knockout; Mutation; Neuroscience; Phosphorylation; Post-Synaptic Density - metabolism; Postsynaptic density; Postsynaptic density proteins; Protein binding; Proteins; Research Advance; Rodents; Scientific equipment industry; Sex Factors; synaptic plasticity; synGAP; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; Canada; United States; mouse; chemical biology; rat; glutamate receptor; neuroscience; biochemistry; synGAP; synaptic plasticity
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.52656

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 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 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 rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency.