Regulation of LRRK2: insights from structural and biochemical analysis

References

Anand, V.S., Reichling, L.J., Lipinski, K., Stochaj, W., Duan, W., Kelleher, K., Pungaliya, P., Brown, E.L., Reinhart, P.H., Somberg, R., et al. (2009). Investigation of leucine-rich repeat kinase 2: enzymological properties and novel assays. FEBS J. 276, 466–478.10.1111/j.1742-4658.2008.06789.xSuche in Google Scholar PubMed

Atashrazm, F. and Dzamko, N. (2016). LRRK2 inhibitors and their potential in the treatment of Parkinson’s disease: current perspectives. Clin. Pharmacol. Adv. Appl. 8, 177–189.10.2147/CPAA.S102191Suche in Google Scholar

Berger, Z., Smith, K.A., and Lavoie, M.J. (2010). Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry 49, 5511–5523.10.1021/bi100157uSuche in Google Scholar PubMed PubMed Central

Berwick, D.C. and Harvey, K. (2012). LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. Hum. Mol. Genet. 21, 4966–4979.10.1093/hmg/dds342Suche in Google Scholar PubMed PubMed Central

Cookson, M. (2010). The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat. Rev. Neurosci. 11, 791–797.10.1038/nrn2935Suche in Google Scholar PubMed PubMed Central

Dächsel, J.C., Behrouz, B., Yue, M., Beevers, J.E., Melrose, H.L., and Farrer, M.J. (2010). A comparative study of Lrrk2 function in primary neuronal cultures. Parkinsonism Relat. Disord. 16, 650–655.10.1016/j.parkreldis.2010.08.018Suche in Google Scholar PubMed PubMed Central

Deyaert, E., Wauters, L., Guaitoli, G., Konijnenberg, A., Leemans, M., Terheyden, S., Petrovic, A., Gallardo, R., Nederveen-Schippers, L.M., Athanasopoulos, P.S., et al. (2017). A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover. Nat. Commun. 8, 1008.10.1038/s41467-017-01103-4Suche in Google Scholar PubMed PubMed Central

Dzamko, N., Deak, M., Hentati, F., Reith, A.D., Prescott, A.R., Alessi, D.R., and Nichols, R.J. (2010). Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem. J. 430, 405–413.10.1042/BJ20100784Suche in Google Scholar PubMed PubMed Central

Gasper, R., Meyer, S., Gotthardt, K., Sirajuddin, M., and Wittinghofer, A. (2009). It takes two to tango: regulation of G proteins by dimerization. Nat. Rev. Mol. Cell Biol. 10, 423–429.10.1038/nrm2689Suche in Google Scholar PubMed

Gasser, T. (2009). Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev. Mol. Med. 11, 1–20.10.1017/S1462399409001148Suche in Google Scholar PubMed

Gilsbach, B.K., Ho, F.Y., Vetter, I.R., van Haastert, P.J.M., Wittinghofer, A., and Kortholt, A. (2012). Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations. Proc. Natl. Acad. Sci. USA 109, 10322–10327.10.1073/pnas.1203223109Suche in Google Scholar PubMed PubMed Central

Gloeckner, C.J., Kinkl, N., Schumacher, A., Braun, R.J., O’Neill, E., Meitinger, T., Kolch, W., Prokisch, H., and Ueffing, M. (2006). The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet. 15, 223–232.10.1093/hmg/ddi439Suche in Google Scholar PubMed

Gotthardt, K., Weyand, M., Kortholt, A., Van Haastert, P.J.M., and Wittinghofer, A. (2008). Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase. EMBO J. 27, 2239–2249.10.1038/emboj.2008.150Suche in Google Scholar PubMed PubMed Central

Guaitoli, G., Raimondi, F., Gilsbach, B.K., Gómez-Llorente, Y., Deyaert, E., Renzi, F., Li, X., Schaffner, A., Jagtap, P.K., Boldt, K., et al. (2016). Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts. Proc. Natl. Acad. Sci. USA 113, E4357–E4366.10.1073/pnas.1523708113Suche in Google Scholar PubMed PubMed Central

James, N.G., Digman, M.A., Gratton, E., Barylko, B., Ding, X., Albanesi, J.P., Goldberg, M.S., and Jameson, D.M. (2012). Number and brightness analysis of LRRK2 oligomerization in live cells. Biophys. J. 102, L41–43.10.1016/j.bpj.2012.04.046Suche in Google Scholar PubMed PubMed Central

Lewis, P.A., Greggio, E., Beilina, A., Jain, S., Baker, A., and Cookson, M.R. (2007). The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem. Biophys. Res. Commun. 357, 668–671.10.1016/j.bbrc.2007.04.006Suche in Google Scholar PubMed PubMed Central

Marín, I., van Egmond, W.N., and van Haastert, P.J.M. (2008). The Roco protein family: a functional perspective. FASEB J. 22, 3103–3110.10.1096/fj.08-111310Suche in Google Scholar PubMed

Mata, I.F., Wedemeyer, W.J., Farrer, M.J., Taylor, J.P., and Gallo, K.A. (2006). LRRK2 in Parkinson’s disease: protein domains and functional insights. Trends Neurosci. 29, 286–293.10.1016/j.tins.2006.03.006Suche in Google Scholar PubMed

Mata, I.F., Davis, M.Y., Lopez, A.N., Dorschner, M.O., Martinez, E., Yearout, D., Cholerton, B.A., Hu, S.C., Edwards, K.L., Bird, T.D., et al. (2016). The discovery of LRRK2 p.R1441S, a novel mutation for Parkinson’s disease, adds to the complexity of a mutational hotspot. Am. J. Med. Genet. B Neuropsychiatr. Genet. 171, 925–930.10.1002/ajmg.b.32510Suche in Google Scholar PubMed

Nichols, R.J., Dzamko, N., Morrice, N.A., Campbell, D.G., Deak, M., Ordureau, A., Macartney, T., Tong, Y., Shen, J., Prescott, A.R., et al. (2010). 14-3-3 Binding to LRRK2 is disrupted by multiple Parkinson’s disease-associated mutations and regulates cytoplasmic localization. Biochem. J. 430, 393–404.10.1042/BJ20100483Suche in Google Scholar PubMed PubMed Central

Papkovskaia, T.D., Chau, K.-Y., Inesta-Vaquera, F., Papkovsky, D.B., Healy, D.G., Nishio, K., Staddon, J., Duchen, M.R., Hardy, J., Schapira, A.H., et al. (2012). G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum. Mol. Genet. 21, 4201–4213.10.1093/hmg/dds244Suche in Google Scholar PubMed PubMed Central

Purlyte, E., Dhekne, H.S., Sarhan, A.R., Gomez, R., Lis, P., Wightman, M., Martinez, T.N., Tonelli, F., Pfeffer, S.R., and Alessi, D.R. (2018). Rab29 activation of the Parkinson’s disease-associated LRRK2 kinase. EMBO J. 37, 1–18.10.15252/embj.201798099Suche in Google Scholar PubMed PubMed Central

Ray, S., Bender, S., Kang, S., Lin, R., Glicksman, M.A., and Liu, M. (2014). The Parkinson disease-linked LRRK2 protein mutation I2020T stabilizes an active state conformation leading to increased kinase activity. J. Biol. Chem. 289, 13042–13053.10.1074/jbc.M113.537811Suche in Google Scholar PubMed PubMed Central

Reichling, L.J. and Riddle, S.M. (2009). Leucine-rich repeat kinase 2 mutants I2020T and G2019S exhibit altered kinase inhibitor sensitivity. Biochem. Biophys. Res. Commun. 384, 255–258.10.1016/j.bbrc.2009.04.098Suche in Google Scholar PubMed

Scheffzek, K. (1997). The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277, 333–338.10.1126/science.277.5324.333Suche in Google Scholar PubMed

Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., et al. (2016). Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5, 1–28.10.7554/eLife.12813Suche in Google Scholar PubMed PubMed Central

Tang, B.L. (2017). Rabs, membrane dynamics, and Parkinson’s disease. J. Cell. Physiol. 232, 1626–1633.10.1002/jcp.25713Suche in Google Scholar PubMed

Taymans, J.-M., Vancraenenbroeck, R., Ollikainen, P., Beilina, A., Lobbestael, E., De Maeyer, M., Baekelandt, V., and Cookson, M.R. (2011). LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding. PLoS One 6, e23207.10.1371/journal.pone.0023207Suche in Google Scholar PubMed PubMed Central

Terheyden, S., Ho, F.Y., Gilsbach, B.K., Wittinghofer, A., and Kortholt, A. (2015). Revisiting the Roco G-protein cycle. Biochem. J. 465, 139–147.10.1042/BJ20141095Suche in Google Scholar PubMed

Thévenet, J., Pescini Gobert, R., Hooft van Huijsduijnen, R., Wiessner, C., and Sagot, Y.J. (2011). Regulation of LRRK2 expression points to a functional role in human monocyte maturation. PLoS One 6, e21519.10.1371/journal.pone.0021519Suche in Google Scholar PubMed PubMed Central

van Egmond, W.N. and van Haastert, P.J.M. (2010). Characterization of the Roco protein family in Dictyostelium discoideum. Eukaryot. Cell 9, 751–761.10.1128/EC.00366-09Suche in Google Scholar PubMed PubMed Central

Vetter, I.R. and Wittinghofer, A. (2001). The guanine nucleotide-binding switch in three dimensions. Science 294, 1299–1304.10.1126/science.1062023Suche in Google Scholar PubMed

West, A.B., Moore, D.J., Biskup, S., Bugayenko, A., Smith, W.W., Ross, C.A., Dawson, V.L., and Dawson, T.M. (2005). Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl. Acad. Sci. USA 102, 16842–16847.10.1073/pnas.0507360102Suche in Google Scholar PubMed PubMed Central

Winner, B., Melrose, H.L., Zhao, C., Hinkle, K.M., Yue, M., Kent, C., Braithwaite, A.T., Ogholikhan, S., Aigner, R., Winkler, J., et al. (2011). Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. Neurobiol. Dis. 41, 706–716.10.1016/j.nbd.2010.12.008Suche in Google Scholar PubMed PubMed Central

Wittinghofer, A. and Vetter, I.R. (2011). Structure-function relationships of the G domain, a canonical switch motif. Annu. Rev. Biochem. 80, 943–971.10.1146/annurev-biochem-062708-134043Suche in Google Scholar PubMed