Apr 13, 2020

In vivo visual screen for dopaminergic Rab {leftrightarrow} LRRK2-G2019S interactions in Drosophila discriminates Rab10 from Rab3

BioRxiv : the Preprint Server for Biology
S. PetridiC. Ugbode

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. Rab10is expressed in dopaminergic neurons controlling vision where Rab3 is undetectable. 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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Mentioned in this Paper

Transposase
Genes
Sequence Determinations, RNA
Question (Inquiry)
Nucleic Acid Sequencing
Sequence Determinations
Gene Amplification Technique
Sequencing
RNA, Small Cytoplasmic
Drop Arm Test

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