PXD050088 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Identifying novel LRRK2 substrates in mouse bone marrow-derived macrophages |
| Description | LRRK2 is commonly mutated in Parkinson’s disease and has cell type-specific mechanisms of activation and function. In macrophages, LRRK2 is associated with lysosomes and is activated following lysosomal damage. However, the functional outcomes of clinically relevant pathogenic mutations in macrophages are unknown. Here, using primary mouse and patient-derived iPSC-derived macrophage (iPSDM) models of LRRK2-G2019S, we defined the substrates of LRRK2 after lysosomal damage. Using phosphoproteomics we found that LRRK2-G2019S and wild-type macrophages showed similar levels of Rab GTPases phosphorylation after lysosomal damage. However, the levels of pRab12 increased whereas the levels of pRab35 decreased in LRRK2-G2019S macrophages. Functionally, LRRK2-G2019S macrophages showed a deficit in lysosomal membrane repair that resulted in more cell death and increased apoptosis. Importantly, we recapitulated this phenotype in iPSDM from patients carrying the G2019S mutation, but not in isogenic control iPSDM. Altogether, we define here the signaling downstream of G2019S in macrophages and identify susceptibility to cell death after lysosomal damage as an important phenotype of this mutation. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-07-10 |
| AnnouncementXML | Submission_2026-07-09_17:51:02.593.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Simeon Mihaylov |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | phosphorylated residue |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-02-23 08:39:51 | ID requested | |
| ⏵ 1 | 2026-07-09 17:51:03 | announced | |
Publication List
Keyword List
| submitter keyword: lysosome,LRRK2, BMDM, lysosomal damage, mouse |
Contact List
| Sila Konur Ultanir |
|---|
| contact affiliation | Kinases and Brain Development Lab, The Francis Crick Institute, England |
| contact email | sila.ultanir@crick.ac.uk |
| lab head | |
| Simeon Mihaylov |
|---|
| contact affiliation | The Francis Crick Institute |
| contact email | simeon.mihaylov@crick.ac.uk |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050088
- Label: PRIDE project
- Name: Identifying novel LRRK2 substrates in mouse bone marrow-derived macrophages
