PXD056498

PXD056498 is an original dataset announced via ProteomeXchange.

Title	The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles
Description	While it is known that endocannabinoids (eCB) modulate multiple neuronal functions, the molecular mechanism governing their release and transport remains elusive. Here, we propose an “on demand release” model, wherein the formation of microvesicles, a specific group of extracellular vesicles (EVs) containing the eCB, 2-arachidonoylglycerol (2-AG), is the rate-limiting step. A co31 culture model system that combines a reporter cell line expressing the fluorescent eCB sensor,GRABeCB2.0, and neuronal cells revealed that neurons release EVs containing 2-AG, but not anandamide, in a stimulus-dependent process regulated by PKC, DAGL, Arf6, and which was sensitive to inhibitors of eCB facilitated diffusion. A vesicle contained approximately 2000 2-AG molecules. Accordingly, hippocampal eCB-mediated synaptic plasticity was modulated by Arf6 and transport inhibitors. This “on demand release” model, supported by mathematical analysis, offers a cohesive framework for understanding eCB signaling at the molecular level and suggests that microvesicles carrying signaling lipids regulate neuronal functions in parallel to canonical synaptic vesicles. To show the identity and purity of the EVs isolated in this study, the proteome of the EVs and their parental cells were analyzed by LC-MS/MS
HostingRepository	PRIDE
AnnounceDate	2025-02-27
AnnouncementXML	Submission_2025-02-27_03:52:14.875.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Verena Straub
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	L-cysteine methyl disulfide
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-04 05:51:38	ID requested
⏵ 1	2025-02-27 03:52:15	announced

10.1073/PNAS.2421717122;

submitter keyword: endocannabinoid, extracellular vesicle, diacylglycerol lipase, 2-AG, cannabinoid 1 receptors

Mario van der Stelt
contact affiliation	Department of Molecular Physiology, Leiden University & Oncode Institute, The Netherlands
contact email	m.van.der.stelt@chem.leidenuniv.nl
lab head
Verena Straub
contact affiliation	Leiden University
contact email	v.m.straub@lic.leidenuniv.nl
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/2025/02/PXD056498

PRIDE project URI

• PRIDE
  1. PXD056498
     1. Label: PRIDE project
     2. Name: The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles