Protein SUMOylation is a sex-specific regulator of fear memory formation in the amygdala

Behav Brain Res. 2022 May 18:113928. doi: 10.1016/j.bbr.2022.113928. Online ahead of print.ABSTRACTStrong evidence has implicated ubiquitin signaling in the process of fear memory formation. While less abundant than ubiquitination, evidence suggests that protein SUMOylation may also be involved in fear memory formation in neurons. However, the importance of amygdala protein SUMOylation in fear memory formation has never been directly examined. Furthermore, while recent evidence indicates that males and females differ significantly in the requirement for ubiquitin signaling during fear memory formation, whether sex differences also exist in the importance of protein SUMOylation to this process remains unknown. Here we found that males and females differ in the requirement for protein SUMOylation in the amygdala during fear memory formation. Western blot analysis revealed that while females had higher resting levels of SUMOylation, both sexes showed global increases following fear conditioning. However, SUMOylation-specific proteomic analysis revealed that only females have increased targeting of individual proteins by SUMOylation following fear conditioning, some of which were heat shock proteins. This suggests that protein SUMOylation is more robustly engaged in the amygdala of females following fear conditioning. In vivo siRNA mediated knockdown of Ube2i, the coding gene for the essential E2 ligase for SUMOylation conjugation, in the amygdala impaired fear memory in males wi...

Source: Brain Research - May 21, 2022 Category: Neurology Authors: Aspen Gustin Shaghayegh Navabpour Kayla Farrell Kiley Martin Jessica DuVall W Keith Ray Richard F Helm Timothy J Jarome Source Type: research