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

Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; International Parkinson’s Disease Genomics Consortium; North American Brain Expression Consortium; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin

doi:10.1073/pnas.1318306111

Cited by 348

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

Beilina, Alexandria, Rudenko, Iakov N., Kaganovich, Alice, Civiero, Laura, Chau, Hien, Kalia, Suneil K., Kalia, Lorraine V., Lobbestael, Evy, Chia, Ruth, Ndukwe, Kelechi, Ding, Jinhui, Nalls, Mike A., International Parkinson’s Disease Genomics Consortium, North American Brain Expression Consortium, Olszewski, Maciej, Hauser, David N., Kumaran, Ravindran, Lozano, Andres M., Baekelandt, Veerle, Greene, Lois E., Taymans, Jean-Marc, Greggio, Elisa, Cookson, Mark R., Nalls, Mike A., Plagnol, Vincent, Martinez, Maria, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gibbs, J Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Gústafsson, Ómar, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Illig, Thomas, München, Helmholtz Zentrum, Jónsson, Pálmi V, Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, München, Helmholtz Zentrum, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, Mudanohwo, Ese, O’Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Hardy, John, Heutink, Peter, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B, Wood, Nicholas W, Chinnery, Patrick F, Arepalli, Sampath, Cookson, Mark R, Dillman, Allissa, Ferrucci, Luigi, Gibbs, J Raphael, Hernandez, Dena G, Johnson, Robert, Longo, Dan L, Majounie, Elisa, Nalls, Michael A, O’Brien, Richard, Singleton, Andrew B, Traynor, Bryan J, Troncoso, Juan, van der Brug, Marcel, Zielke, H Ronald, Zonderman, Alan B·2014·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1318306111

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Abstract

Significance: Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification of protein–protein interactions can help determine the most likely candidate for several GWAS loci. This result illustrates a significant general principle that will likely apply across multiple diseases.

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Other studies reported a physical interaction between LRRK2 and RAB29, and when overexpressed, RAB29 can recruit LRRK2 to the Golgi network.
“Other studies have reported a physical interaction between LRRK2 and RAB29, and when overexpressed, RAB29 can recruit LRRK2 to the Golgi network [23,54,55,56].”
From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [23]
Two mutant RAB29 versions previously described to cause RAB29 inactivation did not rescue the LRRK2-mediated endolysosomal trafficking deficits.
“In contrast, two mutant RAB29 versions previously described to cause RAB29 inactivation [23,54,55] did not rescue the LRRK2-mediated endolysosomal trafficking deficits (Figure 5B,C).”
From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [23]
The reported recruitment of LRRK2 to the Golgi complex by RAB29 is only observed when RAB29 is overexpressed to a larger extent.
“Finally, our data show that the reported recruitment of LRRK2 to the Golgi complex by RAB29 [23,54,55,56] is only observed when RAB29 is overexpressed to a larger extent.”
From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [23]

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Authors: 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., International Parkinson’s Disease Genomics Consortium, North American Brain Expression Consortium, Olszewski, M., Hauser, D. N., Kumaran, R., Lozano, A. M., Baekelandt, V., Greene, L. E., Taymans, J.-M., Greggio, E., Cookson, M. R., Nalls, M. A., Plagnol, V., Martinez, M., Hernandez, D. G., Sharma, M., Sheerin, U.-M., Saad, M., Simón-Sánchez, J., Schulte, C., Lesage, S., Sveinbjörnsdóttir, S., Arepalli, S., Barker, R., Ben-Shlomo, Y., Berendse, H. W., Berg, D., Bhatia, K., de Bie, R. M. A., Biffi, A., Bloem, B., Bochdanovits, Z., Bonin, M., Bras, J. M., Brockmann, K., Brooks, J., Burn, D. J., Charlesworth, G., Chen, H., Chong, S., Clarke, C. E., Cookson, M. R., Cooper, J. M., Corvol, J. C., Counsell, C., Damier, P., Dartigues, J.-F., Deloukas, P., Deuschl, G., Dexter, D. T., van Dijk, K. D., Dillman, A., Durif, F., Dürr, A., Edkins, S., Evans, J. R., Foltynie, T., Gao, J., Gardner, M., Gibbs, J. R., Goate, A., Gray, E., Guerreiro, R., Gústafsson, Ó., Harris, C., van Hilten, J. J., Hofman, A., Hollenbeck, A., Holton, J., Hu, M., Huang, X., Huber, H., Hudson, G., Hunt, S. E., Huttenlocher, J., Illig, T., München, H. Z., Jónsson, P. V., Lambert, J.-C., Langford, C., Lees, A., Lichtner, P., München, H. Z., Limousin, P., Lopez, G., Lorenz, D., McNeill, A., Moorby, C., Moore, M., Morris, H. R., Morrison, K. E., Mudanohwo, E., O’Sullivan, S. S., Pearson, J., Perlmutter, J. S., Pétursson, 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, C. C. A., Stefánsson, H., Steinberg, S., Stockton, J. D., Strange, A., Talbot, K., Tanner, C. M., Tashakkori-Ghanbaria, A., Tison, F., Trabzuni, D., Traynor, B. J., Uitterlinden, A. G., Velseboer, D., Vidailhet, M., Walker, R., van de Warrenburg, B., Wickremaratchi, M., Williams, N., Williams-Gray, C. H., Winder-Rhodes, S., Stefánsson, K., Hardy, J., Heutink, P., Brice, A., Gasser, T., Singleton, A. B., Wood, N. W., Chinnery, P. F., Arepalli, S., Cookson, M. R., Dillman, A., Ferrucci, L., Gibbs, J. R., Hernandez, D. G., Johnson, R., Longo, D. L., Majounie, E., Nalls, M. A., O’Brien, R., Singleton, A. B., Traynor, B. J., Troncoso, J., van der Brug, M., Zielke, H. R., & Zonderman, A. B.
Affiliations: Cell Biology and Gene Expression Section,
Department of Biology, University of Padova, 35131 Padua, Italy;
Division of Brain, Imaging, and Behaviour Systems Neuroscience,
Division of Neurosurgery, Department of Surgery, and
Division of Neurology, Department of Medicine, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada M5T 2S8;
Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000 Leuven, Belgium;
Computational Biology Core, Laboratory of Neurogenetics, and
Laboratory of Cellular Physiology, National Heart, Lung and Blood Institute/National Institutes of Health, Bethesda, MD 20892; and
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2014-02-07
Volume: 111
Issue: 7
Pages: 2626-2631
ISSN: 0027-8424
1091-6490
DOI: 10.1073/pnas.1318306111
Cited by: 348
References: 3
Language: en

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

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