LRRK2 mediates tubulation and vesicle sorting from lysosomes
| العنوان: | LRRK2 mediates tubulation and vesicle sorting from lysosomes |
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| المؤلفون: | Alexandra Beilina, Ravindran Kumaran, Christopher K. E. Bleck, Natalie Landeck, Yan Li, Jillian H. Kluss, Sara Saez-Atienzar, Eric Lindberg, Adamantios Mamais, Mark R. Cookson, Luis Bonet-Ponce, Chad D. Williamson |
| المصدر: | Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Proteomics, Lysosomal membrane, Diseases and Disorders, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, 03 medical and health sciences, 0302 clinical medicine, Lysosome, medicine, Phosphorylation, Research Articles, 030304 developmental biology, LRRK2 Gene, 0303 health sciences, Multidisciplinary, Chemistry, Vesicle, SciAdv r-articles, Signal transducing adaptor protein, Cell Biology, LRRK2, nervous system diseases, Cell biology, Protein Transport, medicine.anatomical_structure, Mutation, Lysosomes, 030217 neurology & neurosurgery, Research Article |
| الوصف: | The Parkinson disease kinase LRRK2 translocates to the lysosomal membrane triggering lysosomal sorting through JIP4. Genetic variation around the LRRK2 gene affects risk of both familial and sporadic Parkinson’s disease (PD). However, the biological functions of LRRK2 remain incompletely understood. Here, we report that LRRK2 is recruited to lysosomes after exposure of cells to the lysosome membrane–rupturing agent LLOME. Using an unbiased proteomic screen, we identified the motor adaptor protein JIP4 as an LRRK2 partner at the lysosomal membrane. LRRK2 can recruit JIP4 to lysosomes in a kinase-dependent manner via the phosphorylation of RAB35 and RAB10. Using super-resolution live-cell imaging microscopy and FIB-SEM, we demonstrate that JIP4 promotes the formation of LAMP1-negative tubules that release membranous content from lysosomes. Thus, we describe a new process orchestrated by LRRK2, which we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2), by which lysosomal tubulation is used to release vesicles from lysosomes. Given the central role of the lysosome in PD, LYTL is likely to be disease relevant. |
| تدمد: | 2375-2548 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f3fd0ee4c4c81864941322c901d1f50 https://doi.org/10.1126/sciadv.abb2454 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2f3fd0ee4c4c81864941322c901d1f50 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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