PXD047812

PXD047812 is an original dataset announced via ProteomeXchange.

Title	DDHD2 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
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_02:30:26.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Matthews
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-13 19:59:12	ID requested
⏵ 1	2024-05-22 02:30:27	announced

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]

submitter keyword: Phospholipase A1

Free Fatty Acids

Myristic Acid

Learning and Memory,Lipids

Frederic Meunier
contact affiliation	Professor and Academic Senior Group Leader Queensland Brain Institute University of Queensland
contact email	f.meunier@uq.edu.au
lab head
Benjamin Matthews
contact affiliation	Queensland Brain Institute University of Queensland
contact email	benjamin.matthews@uq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047812
     1. Label: PRIDE project
     2. Name: DDHD2 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