In Vivo Visual Screen for Dopaminergic Rab ↔ LRRK2-G2019S Interactions in Drosophila Discriminates Rab10 from Rab3
| العنوان: | In Vivo Visual Screen for Dopaminergic Rab ↔ LRRK2-G2019S Interactions in Drosophila Discriminates Rab10 from Rab3 |
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| المؤلفون: | Stavroula Petridi, Alison Fellgett, Chris Ugbode, Christopher J. H. Elliott, C. A. Middleton, Laura E. Covill |
| المصدر: | G3: Genes, Genomes, Genetics, Vol 10, Iss 6, Pp 1903-1914 (2020) G3: Genes|Genomes|Genetics |
| بيانات النشر: | Oxford University Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | parkinson’s disease, GTPase, QH426-470, drosophila melanogaster, rab3, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Genetics, Kinase activity, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, parkinson’s uk k-1704 g-1804, biology, Neurodegeneration, Dopaminergic, Mutant Screen Report, In vitro toxicology, rab10, biology.organism_classification, medicine.disease, LRRK2, Cell biology, nervous system diseases, Rab, Drosophila melanogaster, 030217 neurology & neurosurgery, g2019s, lrrk2 |
| الوصف: | LRRK2 mutations cause Parkinson’s, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previous in vitro assays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesis in vivo in a functional, electroretinogram screen, expressing each Rab with/without LRRK2-G2019S in selected Drosophila dopaminergic neurons. Our screen discriminated Rab10 from Rab3. The strongest Rab/LRRK2-G2019S interaction is with Rab10; the weakest with Rab3. Rab10 is expressed in a different set of dopaminergic neurons from Rab3. Thus, anatomical and physiological patterns of Rab10 are related. We conclude that Rab10 is a valid substrate of LRRK2 in dopaminergic neurons in vivo. We propose that variations in Rab expression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson’s. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2160-1836 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31e461e732c40cd9ced67e3b3fe3f339Test http://g3journal.org/lookup/doi/10.1534/g3.120.401289Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31e461e732c40cd9ced67e3b3fe3f339 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21601836 |
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