PT  - JOURNAL ARTICLE
AU  - Stavroula Petridi
AU  - C. Adam Middleton
AU  - Chris Ugbode
AU  - Alison Fellgett
AU  - Laura Covill
AU  - Christopher J. H. Elliott
TI  - <em>In vivo</em> visual screen for dopaminergic <em>Rab ↔ LRRK2-G2019S</em> interactions in <em>Drosophila</em> discriminates <em>Rab10</em> from <em>Rab3</em>
AID  - 10.1101/2020.04.10.035758
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.10.035758
4099  - http://biorxiv.org/content/early/2020/04/13/2020.04.10.035758.short
4100  - http://biorxiv.org/content/early/2020/04/13/2020.04.10.035758.full
AB  - 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.