In Vivo Visual Screen for Dopaminergic Rab ↔ LRRK2-G2019S Interactions in Drosophila Discriminates Rab10 from Rab3
Open Access
- 1 June 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in G3 Genes|Genomes|Genetics
- Vol. 10 (6), 1903-1914
- https://doi.org/10.1534/g3.120.401289
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.This publication has 72 references indexed in Scilit:
- Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energyHuman Molecular Genetics, 2013
- Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytesThe Journal of cell biology, 2012
- Rab32 Is Important for Autophagy and Lipid Storage in DrosophilaPLOS ONE, 2012
- Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioningHuman Molecular Genetics, 2011
- Systematic Discovery of Rab GTPases with Synaptic Functions in DrosophilaCurrent Biology, 2011
- Design Principles of Insect and Vertebrate Visual SystemsNeuron, 2010
- Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in DrosophilaJournal of Neuroscience, 2009
- Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three QuestionsASN Neuro, 2009
- A Drosophila model for LRRK2 -linked parkinsonismProceedings of the National Academy of Sciences of the United States of America, 2008
- RAB-10 Regulates Glutamate Receptor Recycling in a Cholesterol-dependent Endocytosis PathwayMolecular Biology of the Cell, 2007