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In Vivo Visual Screen for Dopaminergic Rab ↔ LRRK2-G2019S Interactions in Drosophila Discriminates Rab10 from Rab3.
Petridi, Stavroula; Middleton, C Adam; Ugbode, Chris; Fellgett, Alison; Covill, Laura; Elliott, Christopher J H.
Afiliação
  • Petridi S; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.
  • Middleton CA; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.
  • Ugbode C; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.
  • Fellgett A; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.
  • Covill L; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.
  • Elliott CJH; Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK cje2@york.ac.uk.
G3 (Bethesda) ; 10(6): 1903-1914, 2020 06 01.
Article em En | MEDLINE | ID: mdl-32321836
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Drosophila Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Drosophila Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article