Abstract
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Highlights
The cause of most Parkinson’s disease remains unknown, autosomal dominant mutations in the leucine rich repeat kinase 2 (LRRK2) gene account for 1–2% of all cases and lead to activation of the LRRK2 kinase (Alessi and Sammler, 2018)
To explore the relationship between primary cilia and two important LRRK2 substrates, we revisited the contributions of Rab8A and Rab10 to primary cilia formation
The effects of Rab8A or Rab10 knockout on primary cilia formation were reversed upon re-expression of exogenous Rab8A or Rab10 wild type proteins (Figure 1D,E; Rab10,~4 fold overexpressed and Rab8A,~10 fold): exogenous Rab8A stimulated while Rab10 inhibited ciliogenesis in cells lacking these proteins
Summary
The cause of most Parkinson’s disease remains unknown, autosomal dominant mutations in the leucine rich repeat kinase 2 (LRRK2) gene account for 1–2% of all cases (and 18% of cases in those of Ashkenazi Jewish descent) and lead to activation of the LRRK2 kinase (Alessi and Sammler, 2018). Unlike Rab8A, Rab is a native suppressor of ciliogenesis, and upon LRRK2 phosphorylation, it binds preferentially to RILPL1 (Rab interacting lysosomal protein-like 1) protein to further interfere with cilia formation. These cilia modulatory events have important consequences in the brain where they influence the ability of cholinergic neurons to generate cilia in the somatosensory cortex; loss of cilia will decrease the ability of these neurons to respond to a Sonic hedgehog signal that triggers neuroprotective signaling toward dopaminergic circuits (Gonzalez-Reyes et al, 2012)
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