PXD065808-1

PXD065808 is an original dataset announced via ProteomeXchange.

Title	Sex and experience dependent regulation of synaptic protein turnover
Description	Synaptic transmission can be carefully tuned through plasticity mechanisms that regulate synaptic strength, structure, and number. In vivo measurements demonstrate remarkable spine dynamics, with subsets of synapses persisting for months. This correlates with the extreme longevity of certain memories, that can persist for an organism’s lifetime. The molecular basis supporting the long-term stability of certain synapses and the long-term durability of memories remain unknown. At the protein level, most proteins persist for a relatively short amount of time before they are degraded and replaced with new molecules. However, recent work has identified a population of proteins, including those present at the synapse, that are exceptionally long-lived. It has been speculated that long-lived proteins (LLPs) could contribute to long-term synapse stability, function, and memory. Here we used stable isotope labeling in mammals (SILAM) to first identify LLPs in the post synaptic density (PSD) of the hippocampus and subsequently determine if protein turnover rates varied by sex or following learning. We identified novel synaptic LLPs and also found that both sex and experience can regulate synaptic protein turnover rates. We identified sex-dependent changes in protein turnover rates in autism spectrum disorder (ASD) risk genes, including increased stability of Gabrg2, a GABA-A receptor subunit, in male mice. Furthermore, we observed stabilization of a subset of PSD proteins, such as Shank3, following contextual fear conditioning. We propose that sex and experience dependent changes in protein turnover rates could help explain sex-differences in psychiatric risk and aid our understanding of the molecular mechanisms that support learning and memory.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_17:25:22.512.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	6x(13)C labeled residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-05 23:02:16	ID requested
⏵ 1	2026-09-06 17:25:23	announced

10.1073/pnas.2602111123;

Heo S, Zhang S, Mun DG, Pandey A, Bygrave AM, Huganir RL, Sex- and experience-dependent regulation of synaptic protein turnover. Proc Natl Acad Sci U S A, 123(28):e2602111123(2026) [pubmed]

submitter keyword: SILAM, Protein turnover, LC-MS/MS

Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, USA
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065808
     1. Label: PRIDE project
     2. Name: Sex and experience dependent regulation of synaptic protein turnover