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

A. Beilina; I.N. Rudenko; A. Kaganovich; L. Civiero; H. Chau; S.K. Kalia; L.V. Kalia; E. Lobbestael; R. Chia; K. Ndukwe; J. Ding; M.A. Nalls; M. Olszewski; D.N. Hauser; R. Kumaran; A.M. Lozano; V. Baekelandt; L.E. Greene; J.-M. Taymans; E. Greggio; M.R. Cookson; V. Plagnol; M. Martinez; D.G. Hernandez; M. Sharma; U.-M. Sheerin; M. Saad; J. Simon-Sanchez; C. Schulte; S. Lesage; S. Sveinbjornsdottir; S. Arepalli; R. Barker; Y. Ben-Shlomo; H.W. Berendse; D. Berg; K. Bhatia; R.M.A. de Bie; A. Biffi; B. Bloem; Z. Bochdanovits; M. Bonin; J.M. Bras; K. Brockmann; J. Brooks; D.J. Burn; G. Charlesworth; H. Chen; S. Chong; C.E. Clarke; J.M. Cooper; J.C. Corvol; C. Counsell; P. Damier; J.-F. Dartigues; P. Deloukas; G. Deuschl; D.T. Dexter; K.D. van Dijk; A. Dillman; F. Durif; A. Durr; S. Edkins; J.R. Evans; T. Foltynie; J. Gao; M. Gardner; J.R. Gibbs; A. Goate; E. Gray; R. Guerreiro; O. Gustafsson; C. Harris; J.J. van Hilten; A. Hofman; A. Hollenbeck; J. Holton; M. Hu; X. Huang; H. Huber; G. Hudson; S.E. Hunt; J. Huttenlocher; T. Illig; H.Z. Munchen; P.V. Jonsson; J.-C. Lambert; C. Langford; A. Lees; P. Lichtner; P. Limousin; G. Lopez; D. Lorenz; A. McNeill; C. Moorby; M. Moore; Huw R Morris; K.E. Morrison; E. Mudanohwo; S.S. O'Sullivan; J. Pearson; J.S. Perlmutter; H. Petursson; P. Pollak; B. Post; S. Potter; B. Ravina; T. Revesz; O. Riess; F. Rivadeneira; P. Rizzu; M. Ryten; S. Sawcer; A. Schapira; H. Scheffer; K. Shaw; I. Shoulson; E. Sidransky; C. Smith; C.C.A. Spencer; H. Stefansson; S. Steinberg; J.D. Stockton; A. Strange; K. Talbot; C.M. Tanner; A. Tashakkori-Ghanbaria; F. Tison; D. Trabzuni; B.J. Traynor; A.G. Uitterlinden; D. Velseboer; M. Vidailhet; R. Walker; B. van de Warrenburg; M. Wickremaratchi; N. Williams; C.H. Williams-Gray; S. Winder-Rhodes; K. Stefansson; John Hardy; P. Heutink; A. Brice; T. Gasser; A.B. Singleton; N.W. Wood; P.F. Chinnery; L. Ferrucci; R. Johnson; D.L. Longo; E. Majounie; R. O'Brien; J. Troncoso; M. van der Brug; H.R. Zielke; A.B. Zonderman

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, I.N. Rudenko, A. Kaganovich, L. Civiero, H. Chau, S.K. Kalia, L.V. Kalia, E. Lobbestael, R. Chia, K. Ndukwe, J. Ding, M.A. Nalls, M. Olszewski, D.N. Hauser, R. Kumaran, A.M. Lozano, V. Baekelandt, L.E. Greene, J.-M. Taymans, E. GreggioM.R. Cookson, V. Plagnol, M. Martinez, D.G. Hernandez, M. Sharma, U.-M. Sheerin, M. Saad, J. Simon-Sanchez, C. Schulte, S. Lesage, S. Sveinbjornsdottir, S. Arepalli, R. Barker, Y. Ben-Shlomo, H.W. Berendse, D. Berg, K. Bhatia, R.M.A. de Bie, A. Biffi, B. Bloem, Z. Bochdanovits, M. Bonin, J.M. Bras, K. Brockmann, J. Brooks, D.J. Burn, G. Charlesworth, H. Chen, S. Chong, C.E. Clarke, J.M. Cooper, J.C. Corvol, C. Counsell, P. Damier, J.-F. Dartigues, P. Deloukas, G. Deuschl, D.T. Dexter, K.D. van Dijk, A. Dillman, F. Durif, A. Durr, S. Edkins, J.R. Evans, T. Foltynie, J. Gao, M. Gardner, J.R. Gibbs, A. Goate, E. Gray, R. Guerreiro, O. Gustafsson, C. Harris, J.J. van Hilten, A. Hofman, A. Hollenbeck, J. Holton, M. Hu, X. Huang, H. Huber, G. Hudson, S.E. Hunt, J. Huttenlocher, T. Illig, H.Z. Munchen, P.V. Jonsson, J.-C. Lambert, C. Langford, A. Lees, P. Lichtner, P. Limousin, G. Lopez, D. Lorenz, A. McNeill, C. Moorby, M. Moore, Huw R Morris, K.E. Morrison, E. Mudanohwo, S.S. O'Sullivan, J. Pearson, J.S. Perlmutter, H. Petursson, P. Pollak, B. Post, S. Potter, B. Ravina, T. Revesz, O. Riess, F. Rivadeneira, P. Rizzu, M. Ryten, S. Sawcer, A. Schapira, H. Scheffer, K. Shaw, I. Shoulson, E. Sidransky, C. Smith, C.C.A. Spencer, H. Stefansson, S. Steinberg, J.D. Stockton, A. Strange, K. Talbot, C.M. Tanner, A. Tashakkori-Ghanbaria, F. Tison, D. Trabzuni, B.J. Traynor, A.G. Uitterlinden, D. Velseboer, M. Vidailhet, R. Walker, B. van de Warrenburg, M. Wickremaratchi, N. Williams, C.H. Williams-Gray, S. Winder-Rhodes, K. Stefansson, John Hardy, P. Heutink, A. Brice, T. Gasser, A.B. Singleton, N.W. Wood, P.F. Chinnery, L. Ferrucci, R. Johnson, D.L. Longo, E. Majounie, R. O'Brien, J. Troncoso, M. van der Brug, H.R. Zielke, A.B. Zonderman

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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	English
Pages (from-to)	2626-2631
Number of pages	6
Journal	Proceedings of the National Academy of Sciences
Volume	111
Issue number	7
DOIs	https://doi.org/10.1073/pnas.1318306111
Publication status	Published - 18 Feb 2014

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10.1073/pnas.1318306111

Delineating mechanisms which underlie differential cell fates induced by p53 activation and HDAC inhibition in colorectal cancer
Lees, A. (Author), McDade, S. (Supervisor) & Longley, D. (Supervisor), Dec 2021
Student thesis: Doctoral Thesis › Doctor of Philosophy

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Beilina, A., Rudenko, I. N., Kaganovich, A., Civiero, L., Chau, H., Kalia, S. K., Kalia, L. V., Lobbestael, E., Chia, R., Ndukwe, K., Ding, J., Nalls, M. A., Olszewski, M., Hauser, D. N., Kumaran, R., Lozano, A. M., Baekelandt, V., Greene, L. E., Taymans, J.-M., ... Zonderman, A. B. (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, 111(7), 2626-2631. https://doi.org/10.1073/pnas.1318306111

@article{b0276d2734c3435f8801d7258956cc6e,

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 I.N. Rudenko and A. Kaganovich and L. Civiero and H. Chau and S.K. Kalia and L.V. Kalia and E. Lobbestael and R. Chia and K. Ndukwe and J. Ding and M.A. Nalls and M. Olszewski and D.N. Hauser and R. Kumaran and A.M. Lozano and V. Baekelandt and L.E. Greene and J.-M. Taymans and E. Greggio and M.R. Cookson and V. Plagnol and M. Martinez and D.G. Hernandez and M. Sharma and U.-M. Sheerin and M. Saad and J. Simon-Sanchez and C. Schulte and S. Lesage and S. Sveinbjornsdottir and S. Arepalli and R. Barker and Y. Ben-Shlomo and H.W. Berendse and D. Berg and K. Bhatia and {de Bie}, R.M.A. and A. Biffi and B. Bloem and Z. Bochdanovits and M. Bonin and J.M. Bras and K. Brockmann and J. Brooks and D.J. Burn and G. Charlesworth and H. Chen and S. Chong and C.E. Clarke and J.M. Cooper and J.C. Corvol and C. Counsell and P. Damier and J.-F. Dartigues and P. Deloukas and G. Deuschl and D.T. Dexter and {van Dijk}, K.D. and A. Dillman and F. Durif and A. Durr and S. Edkins and J.R. Evans and T. Foltynie and J. Gao and M. Gardner and J.R. Gibbs and A. Goate and E. Gray and R. Guerreiro and O. Gustafsson and C. Harris and {van Hilten}, J.J. and A. Hofman and A. Hollenbeck and J. Holton and M. Hu and X. Huang and H. Huber and G. Hudson and S.E. Hunt and J. Huttenlocher and T. Illig and H.Z. Munchen and P.V. Jonsson and J.-C. Lambert and C. Langford and A. Lees and P. Lichtner and P. Limousin and G. Lopez and D. Lorenz and A. McNeill and C. Moorby and M. Moore and Morris, {Huw R} and K.E. Morrison and E. Mudanohwo and S.S. O'Sullivan and J. Pearson and J.S. Perlmutter and H. Petursson and P. Pollak and B. Post and S. Potter and B. Ravina and T. Revesz and O. Riess and F. Rivadeneira and P. Rizzu and M. Ryten and S. Sawcer and A. Schapira and H. Scheffer and K. Shaw and I. Shoulson and E. Sidransky and C. Smith and C.C.A. Spencer and H. Stefansson and S. Steinberg and J.D. Stockton and A. Strange and K. Talbot and C.M. Tanner and A. Tashakkori-Ghanbaria and F. Tison and D. Trabzuni and B.J. Traynor and A.G. Uitterlinden and D. Velseboer and M. Vidailhet and R. Walker and {van de Warrenburg}, B. and M. Wickremaratchi and N. Williams and C.H. Williams-Gray and S. Winder-Rhodes and K. Stefansson and John Hardy and P. Heutink and A. Brice and T. Gasser and A.B. Singleton and N.W. Wood and P.F. Chinnery and L. Ferrucci and R. Johnson and D.L. Longo and E. Majounie and R. O'Brien and J. Troncoso and {van der Brug}, M. and H.R. Zielke and A.B. Zonderman",

year = "2014",

month = feb,

day = "18",

doi = "10.1073/pnas.1318306111",

language = "English",

volume = "111",

pages = "2626--2631",

journal = "Proceedings of the National Academy of Sciences",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "7",

}

Beilina, A, Rudenko, IN, Kaganovich, A, Civiero, L, Chau, H, Kalia, SK, Kalia, LV, Lobbestael, E, Chia, R, Ndukwe, K, Ding, J, Nalls, MA, Olszewski, M, Hauser, DN, Kumaran, R, Lozano, AM, Baekelandt, V, Greene, LE, Taymans, J-M, Greggio, E, Cookson, MR, Plagnol, V, Martinez, M, Hernandez, DG, Sharma, M, Sheerin, U-M, Saad, M, Simon-Sanchez, J, Schulte, C, Lesage, S, Sveinbjornsdottir, S, Arepalli, S, Barker, R, Ben-Shlomo, Y, Berendse, HW, Berg, D, Bhatia, K, de Bie, RMA, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, Bras, JM, Brockmann, K, Brooks, J, Burn, DJ, Charlesworth, G, Chen, H, Chong, S, Clarke, CE, Cooper, JM, Corvol, JC, Counsell, C, Damier, P, Dartigues, J-F, Deloukas, P, Deuschl, G, Dexter, DT, van Dijk, KD, Dillman, A, Durif, F, Durr, A, Edkins, S, Evans, JR, Foltynie, T, Gao, J, Gardner, M, Gibbs, JR, Goate, A, Gray, E, Guerreiro, R, Gustafsson, O, Harris, C, van Hilten, JJ, Hofman, A, Hollenbeck, A, Holton, J, Hu, M, Huang, X, Huber, H, Hudson, G, Hunt, SE, Huttenlocher, J, Illig, T, Munchen, HZ, Jonsson, PV, Lambert, J-C, Langford, C, Lees, A, Lichtner, P, Limousin, P, Lopez, G, Lorenz, D, McNeill, A, Moorby, C, Moore, M, Morris, HR, Morrison, KE, Mudanohwo, E, O'Sullivan, SS, Pearson, J, Perlmutter, JS, Petursson, H, Pollak, P, Post, B, Potter, S, Ravina, B, Revesz, T, Riess, O, Rivadeneira, F, Rizzu, P, Ryten, M, Sawcer, S, Schapira, A, Scheffer, H, Shaw, K, Shoulson, I, Sidransky, E, Smith, C, Spencer, CCA, Stefansson, H, Steinberg, S, Stockton, JD, Strange, A, Talbot, K, Tanner, CM, Tashakkori-Ghanbaria, A, Tison, F, Trabzuni, D, Traynor, BJ, Uitterlinden, AG, Velseboer, D, Vidailhet, M, Walker, R, van de Warrenburg, B, Wickremaratchi, M, Williams, N, Williams-Gray, CH, Winder-Rhodes, S, Stefansson, K, Hardy, J, Heutink, P, Brice, A, Gasser, T, Singleton, AB, Wood, NW, Chinnery, PF, Ferrucci, L, Johnson, R, Longo, DL, Majounie, E, O'Brien, R, Troncoso, J, van der Brug, M, Zielke, HR & Zonderman, AB 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, vol. 111, no. 7, pp. 2626-2631. https://doi.org/10.1073/pnas.1318306111

TY - JOUR

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, I.N.

AU - Kaganovich, A.

AU - Civiero, L.

AU - Chau, H.

AU - Kalia, S.K.

AU - Kalia, L.V.

AU - Lobbestael, E.

AU - Chia, R.

AU - Ndukwe, K.

AU - Ding, J.

AU - Nalls, M.A.

AU - Olszewski, M.

AU - Hauser, D.N.

AU - Kumaran, R.

AU - Lozano, A.M.

AU - Baekelandt, V.

AU - Greene, L.E.

AU - Taymans, J.-M.

AU - Greggio, E.

AU - Cookson, M.R.

AU - Plagnol, V.

AU - Martinez, M.

AU - Hernandez, D.G.

AU - Sharma, M.

AU - Sheerin, U.-M.

AU - Saad, M.

AU - Simon-Sanchez, J.

AU - Schulte, C.

AU - Lesage, S.

AU - Sveinbjornsdottir, S.

AU - Arepalli, S.

AU - Barker, R.

AU - Ben-Shlomo, Y.

AU - Berendse, H.W.

AU - Berg, D.

AU - Bhatia, K.

AU - de Bie, R.M.A.

AU - Biffi, A.

AU - Bloem, B.

AU - Bochdanovits, Z.

AU - Bonin, M.

AU - Bras, J.M.

AU - Brockmann, K.

AU - Brooks, J.

AU - Burn, D.J.

AU - Charlesworth, G.

AU - Chen, H.

AU - Chong, S.

AU - Clarke, C.E.

AU - Cooper, J.M.

AU - Corvol, J.C.

AU - Counsell, C.

AU - Damier, P.

AU - Dartigues, J.-F.

AU - Deloukas, P.

AU - Deuschl, G.

AU - Dexter, D.T.

AU - van Dijk, K.D.

AU - Dillman, A.

AU - Durif, F.

AU - Durr, A.

AU - Edkins, S.

AU - Evans, J.R.

AU - Foltynie, T.

AU - Gao, J.

AU - Gardner, M.

AU - Gibbs, J.R.

AU - Goate, A.

AU - Gray, E.

AU - Guerreiro, R.

AU - Gustafsson, O.

AU - Harris, C.

AU - van Hilten, J.J.

AU - Hofman, A.

AU - Hollenbeck, A.

AU - Holton, J.

AU - Hu, M.

AU - Huang, X.

AU - Huber, H.

AU - Hudson, G.

AU - Hunt, S.E.

AU - Huttenlocher, J.

AU - Illig, T.

AU - Munchen, H.Z.

AU - Jonsson, P.V.

AU - Lambert, J.-C.

AU - Langford, C.

AU - Lees, A.

AU - Lichtner, P.

AU - Limousin, P.

AU - Lopez, G.

AU - Lorenz, D.

AU - McNeill, A.

AU - Moorby, C.

AU - Moore, M.

AU - Morris, Huw R

AU - Morrison, K.E.

AU - Mudanohwo, E.

AU - O'Sullivan, S.S.

AU - Pearson, J.

AU - Perlmutter, J.S.

AU - Petursson, H.

AU - Pollak, P.

AU - Post, B.

AU - Potter, S.

AU - Ravina, B.

AU - Revesz, T.

AU - Riess, O.

AU - Rivadeneira, F.

AU - Rizzu, P.

AU - Ryten, M.

AU - Sawcer, S.

AU - Schapira, A.

AU - Scheffer, H.

AU - Shaw, K.

AU - Shoulson, I.

AU - Sidransky, E.

AU - Smith, C.

AU - Spencer, C.C.A.

AU - Stefansson, H.

AU - Steinberg, S.

AU - Stockton, J.D.

AU - Strange, A.

AU - Talbot, K.

AU - Tanner, C.M.

AU - Tashakkori-Ghanbaria, A.

AU - Tison, F.

AU - Trabzuni, D.

AU - Traynor, B.J.

AU - Uitterlinden, A.G.

AU - Velseboer, D.

AU - Vidailhet, M.

AU - Walker, R.

AU - van de Warrenburg, B.

AU - Wickremaratchi, M.

AU - Williams, N.

AU - Williams-Gray, C.H.

AU - Winder-Rhodes, S.

AU - Stefansson, K.

AU - Hardy, John

AU - Heutink, P.

AU - Brice, A.

AU - Gasser, T.

AU - Singleton, A.B.

AU - Wood, N.W.

AU - Chinnery, P.F.

AU - Ferrucci, L.

AU - Johnson, R.

AU - Longo, D.L.

AU - Majounie, E.

AU - O'Brien, R.

AU - Troncoso, J.

AU - van der Brug, M.

AU - Zielke, H.R.

AU - Zonderman, A.B.

PY - 2014/2/18

Y1 - 2014/2/18

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

SN - 0027-8424

VL - 111

SP - 2626

EP - 2631

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 7

ER -

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

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Delineating mechanisms which underlie differential cell fates induced by p53 activation and HDAC inhibition in colorectal cancer

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