In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-11-10)
Abstract:
We previously reported that Parkinson’s disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on a conserved residue in their switch-II domains (Steger et al., 2016) (PMID: 26824392). Here, we systematically analyzed the Rab protein family and found 14 of them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation for ten of them (Rab3A/B/C/D, Rab8A/B, Rab10, Rab12, Rab35 and Rab43). Affinity enrichment mass spectrometry revealed that the primary ciliogenesis regulator, RILPL1 specifically interacts with the LRRK2-phosphorylated forms of Rab8A and Rab10, whereas RILPL2 binds to phosphorylated Rab8A, Rab10, and Rab12. Induction of primary cilia formation by serum starvation led to a two-fold reduction in ciliogenesis in fibroblasts derived from pathogenic LRRK2-R1441G knock-in mice. These results implicate LRRK2 in primary ciliogenesis and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.31012.001
DOI:
10.7554/eLife.31012.002
DOI:
10.7554/eLife.31012.003
DOI:
10.7554/eLife.31012.004
DOI:
10.7554/eLife.31012.005
DOI:
10.7554/eLife.31012.006
DOI:
10.7554/eLife.31012.007
DOI:
10.7554/eLife.31012.008
DOI:
10.7554/eLife.31012.009
DOI:
10.7554/eLife.31012.010
DOI:
10.7554/eLife.31012.011
DOI:
10.7554/eLife.31012.012
DOI:
10.7554/eLife.31012.013
DOI:
10.7554/eLife.31012.014
DOI:
10.7554/eLife.31012.015
DOI:
10.7554/eLife.31012.017
DOI:
10.7554/eLife.31012.018
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
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