用于区分多巴胺能相互作用的视觉筛选与……不同

Visual Screen for Dopaminergic Interactions in Discriminates from .

作者信息

Petridi Stavroula, Middleton C Adam, Ugbode Chris, Fellgett Alison, Covill Laura, Elliott Christopher J H

机构信息

Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK.

Department of Biology and York Biomedical Research Institute, University of York, YO1 5DD, UK

出版信息

G3 (Bethesda). 2020 Jun 1;10(6):1903-1914. doi: 10.1534/g3.120.401289.

DOI:10.1534/g3.120.401289

PMID:32321836

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7263684/

Abstract

LRRK2 mutations cause Parkinson's, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previous assays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesis in a functional, electroretinogram screen, expressing each with/without in selected 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 We propose that variations in expression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson's.

摘要

LRRK2突变会导致帕金森病，但从激酶活性增加到病理性神经退行性变的分子联系仍未明确。先前的检测表明，LRRK2的底物至少包括8种Rab GTP酶。我们现在已经在一项功能性视网膜电图筛选中检验了这一假说，在选定的多巴胺能神经元中分别表达带有/不带有（某种情况未明确，原文缺失关键信息）的（相关物质，原文缺失关键信息）。我们的筛选区分了Rab10和Rab3。Rab/LRRK2 - G2019S之间最强的相互作用是与Rab10；最弱的是与Rab3。Rab10在与Rab3不同的一组多巴胺能神经元中表达。因此，Rab10的解剖学和生理学模式是相关的。我们得出结论，Rab10是多巴胺能神经元中LRRK2的有效底物。我们提出，（某种物质，原文缺失关键信息）表达的变化导致了帕金森病中不同多巴胺能核团记录到的神经退行性变速率的差异。