Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

A Beilina; IN Rudenko; A Kaganovich; L Civiero; H Chau; SK Kalia; LV Kalia; E Lobbestael; R Chi; K Ndukwe; J Ding; MA Nalls; M Olszewski; DN Hauser; R Kumaran; AM Lozano; V Baekelandt; LE Greene; JM Taymans; E Greggio; MR Cookson

doi:10.1073/pnas.1318306111

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

A Beilina, IN Rudenko, A Kaganovich, L Civiero, H Chau, SK Kalia, LV Kalia, E Lobbestael, R Chi, K Ndukwe, J Ding, MA Nalls, M Olszewski, DN Hauser, R Kumaran, AM Lozano, V Baekelandt, LE Greene, JM Taymans, E GreggioMR Cookson

Research output: Contribution to journal › Article › Academic › peer-review

301 Citations (Scopus)

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.

Original language	Undefined/Unknown
Pages (from-to)	2626-2631
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the U.S.A.
Volume	111
Issue number	7
DOIs	https://doi.org/10.1073/pnas.1318306111
Publication status	Published - 2014
Externally published	Yes

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EMC NIHES-01-64-01

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1318306111

Cite this

Beilina, A., Rudenko, IN., Kaganovich, A., Civiero, L., Chau, H., Kalia, SK., Kalia, LV., Lobbestael, E., Chi, R., Ndukwe, K., Ding, J., Nalls, MA., Olszewski, M., Hauser, DN., Kumaran, R., Lozano, AM., Baekelandt, V., Greene, LE., Taymans, JM., ... Cookson, MR. (2014). Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proceedings of the National Academy of Sciences of the U.S.A., 111(7), 2626-2631. https://doi.org/10.1073/pnas.1318306111

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title = "Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease",

abstract = "Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.",

author = "A Beilina and IN Rudenko and A Kaganovich and L Civiero and H Chau and SK Kalia and LV Kalia and E Lobbestael and R Chi and K Ndukwe and J Ding and MA Nalls and M Olszewski and DN Hauser and R Kumaran and AM Lozano and V Baekelandt and LE Greene and JM Taymans and E Greggio and MR Cookson",

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Beilina, A, Rudenko, IN, Kaganovich, A, Civiero, L, Chau, H, Kalia, SK, Kalia, LV, Lobbestael, E, Chi, R, Ndukwe, K, Ding, J, Nalls, MA, Olszewski, M, Hauser, DN, Kumaran, R, Lozano, AM, Baekelandt, V, Greene, LE, Taymans, JM, Greggio, E & Cookson, MR 2014, 'Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease', Proceedings of the National Academy of Sciences of the U.S.A., vol. 111, no. 7, pp. 2626-2631. https://doi.org/10.1073/pnas.1318306111

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T1 - Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

AU - Beilina, A

AU - Rudenko, IN

AU - Kaganovich, A

AU - Civiero, L

AU - Chau, H

AU - Kalia, SK

AU - Kalia, LV

AU - Lobbestael, E

AU - Chi, R

AU - Ndukwe, K

AU - Ding, J

AU - Nalls, MA

AU - Olszewski, M

AU - Hauser, DN

AU - Kumaran, R

AU - Lozano, AM

AU - Baekelandt, V

AU - Greene, LE

AU - Taymans, JM

AU - Greggio, E

AU - Cookson, MR

PY - 2014

Y1 - 2014

N2 - Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.

AB - Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.

U2 - 10.1073/pnas.1318306111

DO - 10.1073/pnas.1318306111

M3 - Article

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JO - Proceedings of the National Academy of Sciences of the U.S.A.

JF - Proceedings of the National Academy of Sciences of the U.S.A.

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