Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

Research output: Contribution to journal › Journal article › Research › peer-review

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Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. / Steger, Martin; Diez, Federico; Dhekne, Herschel S; Lis, Pawel; Nirujogi, Raja S; Karayel, Ozge; Tonelli, Francesca; Martinez, Terina N; Lorentzen, Esben; Pfeffer, Suzanne R; Alessi, Dario R; Mann, Matthias.

In: eLife, Vol. 6, 10.11.2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Steger, M, Diez, F, Dhekne, HS, Lis, P, Nirujogi, RS, Karayel, O, Tonelli, F, Martinez, TN, Lorentzen, E, Pfeffer, SR, Alessi, DR & Mann, M 2017, 'Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis', eLife, vol. 6. https://doi.org/10.7554/eLife.31012

APA

Steger, M., Diez, F., Dhekne, H. S., Lis, P., Nirujogi, R. S., Karayel, O., Tonelli, F., Martinez, T. N., Lorentzen, E., Pfeffer, S. R., Alessi, D. R., & Mann, M. (2017). Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. eLife, 6. https://doi.org/10.7554/eLife.31012

Vancouver

Steger M, Diez F, Dhekne HS, Lis P, Nirujogi RS, Karayel O et al. Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. eLife. 2017 Nov 10;6. https://doi.org/10.7554/eLife.31012

Author

Steger, Martin ; Diez, Federico ; Dhekne, Herschel S ; Lis, Pawel ; Nirujogi, Raja S ; Karayel, Ozge ; Tonelli, Francesca ; Martinez, Terina N ; Lorentzen, Esben ; Pfeffer, Suzanne R ; Alessi, Dario R ; Mann, Matthias. / Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. In: eLife. 2017 ; Vol. 6.

Bibtex

@article{c2f79fd896c945df901804ba21522ee2,
title = "Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis",
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.",
keywords = "Journal Article",
author = "Martin Steger and Federico Diez and Dhekne, {Herschel S} and Pawel Lis and Nirujogi, {Raja S} and Ozge Karayel and Francesca Tonelli and Martinez, {Terina N} and Esben Lorentzen and Pfeffer, {Suzanne R} and Alessi, {Dario R} and Matthias Mann",
year = "2017",
month = nov,
day = "10",
doi = "10.7554/eLife.31012",
language = "English",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

AU - Steger, Martin

AU - Diez, Federico

AU - Dhekne, Herschel S

AU - Lis, Pawel

AU - Nirujogi, Raja S

AU - Karayel, Ozge

AU - Tonelli, Francesca

AU - Martinez, Terina N

AU - Lorentzen, Esben

AU - Pfeffer, Suzanne R

AU - Alessi, Dario R

AU - Mann, Matthias

PY - 2017/11/10

Y1 - 2017/11/10

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.7554/eLife.31012

DO - 10.7554/eLife.31012

M3 - Journal article

C2 - 29125462

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

ER -

ID: 186194178