PXD061811-1

PXD061811 is an original dataset announced via ProteomeXchange.

Title	De novo lysine myristoylation mediates synaptic plasticity and long-term potentiation through membrane association of synaptic proteins
Description	Synaptic plasticity underlying long-term memory is associated with the generation of saturated free fatty acids (sFFAs), in particularly myristic acid, from membrane phospholipids via the phospholipase A1 isoform DDHD2. However, the mechanism through which myristic acid contributes to synaptic plasticity remains elusive. Here, we demonstrate that DDHD2-derived myristic acid is rapidly converted to myristoyl CoA, which serves as substrate for N-myristoyl transferases (NMT1/2) to drive post-translational lysine myristoylation of synaptic proteins. Chemically induced long-term potentiation (cLTP) in cortical neurons increases both sFFAs and their CoA conjugates, predominantly myristoyl CoA, a response blocked by the DDHD2 inhibitor KLH-45. Inhibition of DDHD2 (KLH-45) or NMT1/2 (IMP-1088) also disrupts cLTP-induced proteomic changes, impairs dendritic spine remodeling, and prevents LTP in hippocampal slices. Instrumental conditioning also drives proteomic change in the hippocampus, that are abolished in learning-deficient DDHD2-/- mice. Key synaptic proteins, including NMDA receptor subunit GluN1, MAP2, and GAS7, fail to undergo learning-induced changes, effectively linking DDHD2 function to learning-dependent proteome remodeling. Our findings reveal that de novo lysine myristoylation acts to mediate synaptic plasticity and memory formation.
HostingRepository	PRIDE
AnnounceDate	2025-04-22
AnnouncementXML	Submission_2025-04-21_21:40:45.662.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Matthews
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	ZenoTOF 7600; TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-13 19:54:33	ID requested
⏵ 1	2025-04-21 21:40:46	announced

Dataset with its publication pending

submitter keyword: Learning and Memory., Synaptic Plasticity,Lipids

Phospholipase A1

DDHD2

N-myristoyl Transferase

Myristic Acid

Lysine myristoylation

Frédéric A. Meunier
contact affiliation	Queensland Brain Institute, Univerisity 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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD061811

PRIDE project URI

• PRIDE
  1. PXD061811
     1. Label: PRIDE project
     2. Name: De novo lysine myristoylation mediates synaptic plasticity and long-term potentiation through membrane association of synaptic proteins