Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila
| العنوان: | Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila |
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| المؤلفون: | Yuka Hosaka, Takako Morimoto, Yujiro Umezaki, Taku Arano, Hongrui Meng, Tsuyoshi Inoshita, Yuzuru Imai, Hui-Yun Chang, Nobutaka Hattori, Sakiko Kosugi, Masato Koike |
| المصدر: | Human Molecular Genetics. 26:2933-2948 |
| بيانات النشر: | Oxford University Press (OUP), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Retromer, Endosome, Dopamine, Vesicular Transport Proteins, Endosomes, Biology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Synaptic Transmission, Synaptic vesicle, Bulk endocytosis, Animals, Genetically Modified, 03 medical and health sciences, VPS35, 0302 clinical medicine, Genetics, Animals, Drosophila Proteins, Humans, Synaptic vesicle recycling, Molecular Biology, Genetics (clinical), Synaptic vesicle endocytosis, Dopaminergic Neurons, Parkinson Disease, General Medicine, LRRK2, Endocytosis, nervous system diseases, Cell biology, 030104 developmental biology, Mutation, Drosophila, Synaptic Vesicles, 030217 neurology & neurosurgery |
| الوصف: | Mutations of the retromer component Vps35 and endosomal kinase LRRK2 are linked to autosomal dominant forms of familial Parkinson's disease (PD). However, the physiological and pathological roles of Vps35 and LRRK2 in neuronal functions are poorly understood. Here, we demonstrated that the loss of Drosophila Vps35 (dVps35) affects synaptic vesicle recycling, dopaminergic synaptic release and sleep behavior associated with dopaminergic activity, which is rescued by the expression of wild-type dVps35 but not the PD-associated mutant dVps35 D647N. Drosophila LRRK2 dLRRK together with Rab5 and Rab11 is also implicated in synaptic vesicle recycling, and the manipulation of these activities improves the Vps35 synaptic phenotypes. These findings indicate that defects of synaptic vesicle recycling in which two late-onset PD genes, Vps35 and LRRK2, are involved could be key aspects of PD etiology. |
| تدمد: | 1460-2083 0964-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7fc43f2d07da134f23160eb0df425e9Test https://doi.org/10.1093/hmg/ddx179Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c7fc43f2d07da134f23160eb0df425e9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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