{"doi":"10.1101/2020.01.23.917252","title":"LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes","abstract":"ABSTRACT Mutations in the leucine rich repeat kinase 2 ( LRRK2 ) gene are a cause of familial and sporadic Parkinson’s disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recruited to lysosomes that have a ruptured membrane. Using unbiased proteomics, we observed that LRRK2 is able to recruit the motor adaptor protein JIP4 to permeabilized lysosomes in a kinase-dependent manner through the phosphorylation of RAB35 and RAB10. Super-resolution live cell imaging microscopy and FIB-SEM revealed that once at the lysosomal membrane, JIP4 promotes the formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. Released vesicular structures are able to interact with other lysosomes. Thus, we described a new process that uses lysosomal tubulation to release vesicular structures from permeabilized lysosomes. LRRK2 orchestrates this process that we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2) that, given the central role of the lysosome in PD, is likely to be disease relevant.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119602,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238912,"name":"Alexandra Beilina","orcid":null,"position":1,"is_corresponding":false},{"id":236475,"name":"Chad D. Williamson","orcid":"0000-0003-4886-5102","position":2,"is_corresponding":false},{"id":236476,"name":"Eric Lindberg","orcid":"0000-0002-4258-5583","position":3,"is_corresponding":false},{"id":236477,"name":"Jillian H. Kluss","orcid":"0000-0002-6262-6661","position":4,"is_corresponding":false},{"id":236478,"name":"Sara Sáez-Atiénzar","orcid":"0000-0002-1524-9584","position":5,"is_corresponding":false},{"id":236479,"name":"Natalie Landeck","orcid":"0000-0002-8399-4009","position":6,"is_corresponding":false},{"id":238913,"name":"Ravindran Kumaran","orcid":null,"position":7,"is_corresponding":false},{"id":236480,"name":"Adamantios Mamais","orcid":"0000-0002-5546-7084","position":8,"is_corresponding":false},{"id":109646,"name":"Christopher K. E. Bleck","orcid":"0000-0003-1029-3444","position":9,"is_corresponding":false},{"id":236481,"name":"Yan Li","orcid":"0000-0003-3820-5960","position":10,"is_corresponding":false},{"id":238914,"name":"Mark Cookson","orcid":null,"position":11,"is_corresponding":false},{"id":236474,"name":"Luis Bonet‐Ponce","orcid":"0000-0001-9276-059X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:13.002105Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}