ArticleFrontiers in behavioral neuroscience2021
Sex-Specific Linear Polyubiquitination Is a Critical Regulator of Contextual Fear Memory Formation.
Article in Frontiers in behavioral neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Non-canonical K27 polyubiquitination is a sex-specific regulator of contextual fear memory in the hippocampus but not the amygdala.Behavioural brain research · 2026Article
- Temporal- and sex-specific changes in proteasome-dependent and independent polyubiquitination in the amygdala during fear memory formation.Learning & memory (Cold Spring Harbor, N.Y.) · 2026Article
- Linear ubiquitination of the NMDA receptor GluN2A subunit facilitates the GluN2B-to-GluN2A switch and synaptic maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.PloS one · 2024Article
- Sex-differences in proteasome-dependent K48-polyubiquitin signaling in the amygdala are developmentally regulated in rats.Biology of sex differences · 2023Article
- The ubiquitin-proteasome system and learning-dependent synaptic plasticity - A 10 year update.Neuroscience and biobehavioral reviews · 2023Review
- New perspectives on sex differences in learning and memory.Trends in endocrinology and metabolism: TEM · 2023Review
- Proteasome-independent K63 polyubiquitination selectively regulates ATP levels and proteasome activity during fear memory formation in the female amygdala.Molecular psychiatry · 2023Article
- The epigenetic role of proteasome subunit RPT6 during memory formation in female rats.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Protein SUMOylation is a sex-specific regulator of fear memory formation in the amygdala.Behavioural brain research · 2022Article
- Proteomic Analysis Reveals Sex-Specific Protein Degradation Targets in the Amygdala During Fear Memory Formation.Frontiers in molecular neuroscience · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner. Using immunoblot and unbiased proteomic analyses, we found that male (49) and female (14) rats both had increased levels of linear polyubiquitinated substrates following fear conditioning, though none of these protein targets overlapped between sexes. In males, target protein functions involved cell junction and axonal guidance signaling, while in females the primary target was Adiponectin A, a critical regulator of neuroinflammation, synaptic plasticity, and memory, suggesting sex-dependent functional roles for linear polyubiquitination during fear memory formation. Consistent with these increases,
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