PXD028321

PXD028321 is an original dataset announced via ProteomeXchange.

Title	LC-MS/MS proteomics analysis of neuronal cells and secretomes with timsTOF Pro
Description	The neuropeptide VGF was recently proposed as a neurodegeneration biomarker. The Parkinson's disease-related protein leucine-rich repeat kinase 2 (LRRK2) regulates endolysosomal dynamics, a process that involves SNARE-mediated membrane fusion and could regulate secretion. Here we investigate potential biochemical and functional links between LRRK2 and v-SNAREs. We find that LRRK2 directly interacts with the v-SNAREs VAMP4 and VAMP7. Secretomics reveals VGF secretory defects in VAMP4 and VAMP7 knockout (KO) neuronal cells. In contrast, VAMP2 KO "regulated secretion-null" and ATG5 KO "autophagy-null" cells release more VGF. VGF is partially associated with extracellular vesicles and LAMP1+ endolysosomes. LRRK2 expression increases VGF perinuclear localization and impairs its secretion. Retention using selective hooks (RUSH) assays show that a pool of VGF traffics through VAMP4+ and VAMP7+ compartments, and LRRK2 expression delays its transport to the cell periphery. Overexpression of LRRK2 or VAMP7-longin domain impairs VGF peripheral localization in primary cultured neurons. Altogether, our results suggest that LRRK2 might regulate VGF secretion via interaction with VAMP4 and VAMP7.
HostingRepository	PRIDE
AnnounceDate	2023-04-03
AnnouncementXML	Submission_2023-04-03_03:27:08.516.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiaraguerrera
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:25:23	ID requested
1	2023-01-31 12:59:43	announced
⏵ 2	2023-04-03 03:27:08	announced	2023-04-03: Updated project metadata.

Dataset with its publication pending

submitter keyword: VAMPs, parkinson’s disease,Secretome, neuronal cells, timsTOF Pro, LC-MS/MS

ChiaraGuerrera
contact affiliation	Chiara Guerrera, IR1, HDR Head of the Proteomics Platform SFR Necker INSERM US24 Faculty of Medecine, University of Paris 160 rue de Vaugirard 75015 Paris Tél. : 01 40 61 54 67
contact email	chiara.guerrera@inserm.fr
lab head
Chiaraguerrera
contact affiliation	Necker proteomics, INSERM
contact email	chiara.guerrera@inserm.fr
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/2023/01/PXD028321

PRIDE project URI

• PRIDE
  1. PXD028321
     1. Label: PRIDE project
     2. Name: LC-MS/MS proteomics analysis of neuronal cells and secretomes with timsTOF Pro