PXD049984

PXD049984 is an original dataset announced via ProteomeXchange.

Title	Mucolipidosis type IV links TRPML-1 to renal tubulopatia
Description	Loss of function mutations in the lysosomal channel TRPML-1 cause Mucolipidosis type IV, a rare lysosomal storage disease (LSD) characterized by neurological defects, progressive vision loss and achlorhydria.1–4 Recent reports described kidney disease and renal failure in MLIV patients in the second to the third decade of life5, although the molecular mechanisms underlying kidney disease and the physiological role of TRPML-1 in this organ remain unclear. By investigating kidney disease in the mouse model of TRPML-1 KO at different ages, we found an expansion of the lysosomal compartment and the accumulation of autophagic cargo during kidney disease progression. Also, Proximal Tubular Cells (PTCs) from TRPML-1 KO kidneys showed endocytosis defects. In vivo tracing using fluorescent β-Lactoglobulin confirmed a dramatic reduction in apical endocytosis. Excretome analysis of urine revealed that the lack of TRPML-1 results in proteinuria and enzymuria. Interestingly, TRPML-1 KO kidneys present inflammation, preceding lysosomal defects, with a dramatic upregulation of the macrophage markers F4/80 and Galectin-3. Older TRPML-1 KO mice also shown signs of fibrosis. Importantly, we observed a rescue of lysosomal and inflammatory phenotypes in TRPML-1 KO kidneys following AAV-mediated gene transfer of TRPML-1, providing direct evidence of the role of TRPML-1 in kidney function. Altogether, we demonstrate that TRPML-1 is a central player in apical endocytosis and absorptive function in PTCs, explaining kidney disease and opening novel therapeutic opportunities to prevent and treat these alterations in MLIV patients.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_16:17:28.843.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Diego L. Medina
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-21 06:51:51	ID requested
⏵ 1	2026-04-05 16:17:29	announced

10.1681/asn.0000000567;

Grieco G, Montefusco S, Nusco E, Capuozzo A, Cervellini F, Polishchuk E, Bishop M, Miele A, D'Apolito L, La Vecchia C, Aurilia M, Schiavo M, Staiano L, Cesana M, Oberman R, Lynch AV, Musolino P, Trepiccione F, Grishchuk Y, Medina DL, TRPML-1 Dysfunction and Renal Tubulopathy in Mucolipidosis Type IV. J Am Soc Nephrol, 36(4):587-601(2025) [pubmed]

submitter keyword: mucolipidosis, renal, TRMPL

Diego Medina
contact affiliation	TIGEM
contact email	medina@tigem.it
lab head
Diego L. Medina
contact affiliation	Telethon Institue of Genetics and Medicine (TIGEM)
contact email	medina@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/2026/04/PXD049984

PRIDE project URI

• PRIDE
  1. PXD049984
     1. Label: PRIDE project
     2. Name: Mucolipidosis type IV links TRPML-1 to renal tubulopatia