PXD063029-1

PXD063029 is an original dataset announced via ProteomeXchange.

Title	FGF signaling modulates lysosome biogenesis in chondrocytes via the Mannose Phosphate Receptor pathway
Description	The mannose-6-phosphate (M6P) pathway is critical for lysosome biogenesis, facilitating the trafficking of hydrolases to lysosomes to ensure cellular degradative capacity [1], [2]. Fibroblast Growth Factor (FGF) signaling, a key regulator of skeletogenesis [3], has been linked to the autophagy-lysosomal pathway in chondrocytes [4], [5], [6], but its role in lysosome biogenesis remains poorly characterized. Here, using mass spectrometry, lysosome immune-purification, and functional assays, we reveal that chondrocytes lacking FGF receptors 3 and 4 exhibit dysregulations of the M6P pathway, resulting in hypersecretion of lysosomal enzymes and impaired lysosomal function. We found that FGF receptors control the expression of M6P receptors genes in response to FGF stimulation and during cell cycle via TFEB/TFE3 activation. Notably, restoring MPRs function—either through gene expression or activation of TFEB—rescues lysosomal defects in FGFR3;4-deficient chondrocytes. These findings uncover a novel mechanism by which FGF signaling regulates lysosomal function, offering insights into the control of chondrocyte catabolism and the understanding of FGF-related human diseases.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:14:11.628.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Cinque
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-16 06:47:00	ID requested
⏵ 1	2025-08-24 16:14:12	announced

Cinque L, Iavazzo M, Di Bonito G, Polishchuk E, De Cegli R, Settembre C, FGF Signaling Promotes Lysosome Biogenesis in Chondrocytes via the Mannose Phosphate Receptor Pathway. Traffic, 26(7-9):e70013(2025) [pubmed]

10.1111/tra.70013;

submitter keyword: lysosome,FGF,chordrocytes

Laura Cinque
contact affiliation	TIGEM
contact email	l.cinque@tigem.it
lab head
Laura Cinque
contact affiliation	TIGEM
contact email	l.cinque@tigem.it
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/2025/08/PXD063029

PRIDE project URI

• PRIDE
  1. PXD063029
     1. Label: PRIDE project
     2. Name: FGF signaling modulates lysosome biogenesis in chondrocytes via the Mannose Phosphate Receptor pathway