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PXD047812

PXD047812 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDDHD2 interacts with STXBP1 to mediate long-term memory via the generation of saturated free fatty acidsDDHD2 interacts with STXBP1 to mediate long-term memory via the generation of saturated free fatty acids
DescriptionThe phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. Saturated FFAs, particularly myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the DDHD2 isoform of PLA1 in mice markedly reduced saturated FFAs across the brain and memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits. DDHD2 was shown to bind to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1+/- mouse model of STXBP1 encephalopathy that is also associated with intellectual disability and motor dysfunction, we show that STXBP1 controls the targeting of DDHD2 to the plasma membrane and the generation of saturated FFAs in the brain. Our findings suggest key roles for DDHD2 and STXBP1 in the lipid metabolism underlying synaptic plasticity, learning and memory.
HostingRepositoryPRIDE
AnnounceDate2024-05-22
AnnouncementXMLSubmission_2024-05-22_02:30:26.762.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBenjamin Matthews
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListiodoacetamide derivatized residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-12-13 19:59:12ID requested
12024-05-22 02:30:27announced
Publication List
10.1038/s44318-024-00030-7;
Akefe IO, Saber SH, Matthews B, Venkatesh BG, Gormal RS, Blackmore DG, Alexander S, Sieriecki E, Gambin Y, Bertran-Gonzalez J, Vitale N, Humeau Y, Gaudin A, Ellis SA, Michaels AA, Xue M, Cravatt B, Joensuu M, Wallis TP, Meunier FA, The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids. EMBO J, 43(4):533-567(2024) [pubmed]
Keyword List
submitter keyword: Phospholipase A1
Free Fatty Acids
Myristic Acid
Learning and Memory,Lipids
Contact List
Frederic Meunier
contact affiliationProfessor and Academic Senior Group Leader Queensland Brain Institute University of Queensland
contact emailf.meunier@uq.edu.au
lab head
Benjamin Matthews
contact affiliationQueensland Brain Institute University of Queensland
contact emailbenjamin.matthews@uq.edu.au
dataset submitter
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