Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease

Mechanisms of Ageing and Development

Volumn 131, Issue 3, 2010, Pages 210-214

  Dachsel, Justus C ^a   Nishioka, Kenya ^a   Vilariño Güell, Carles ^a   Lincoln, Sarah J ^a   Soto Ortolaza, Alexandra I ^a   Kachergus, Jennifer ^a   Hinkle, Kelly M ^a   Heckman, Michael G ^b   Jasinska Myga, Barbara ^a   Taylor, Julie P ^a   Dickson, Dennis W ^b   Gibson, Rachel A ^c   Hentati, Faycal ^d   Ross, Owen A ^a   Farrer, Matthew J ^a  

^a MAYO GRADUATE SCHOOL   (United States)

^b MAYO CLINIC   (United States)

^c GLAXOSMITHKLINE   (United Kingdom)

^d Institut National de Neurologie Tunisia   (Tunisia)

Author keywords

Dimerization; Genetics; LRRK2; P.G2019S; PD

Indexed keywords

DIMER; GLYCINE; LEUCINE RICH REPEAT KINASE 1; LEUCINE RICH REPEAT KINASE 2; PHOSPHOTRANSFERASE; SERINE; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CONTROLLED STUDY; DIMERIZATION; DISEASE COURSE; FEMALE; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; NUCLEOTIDE SEQUENCE; ONSET AGE; PARKINSON DISEASE; PARKINSONISM; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SYMPTOM; TUNISIA;

AGE OF ONSET; HUMANS; MUTATION; PARKINSON DISEASE; PARKINSONIAN DISORDERS; PENETRANCE; PROTEIN MULTIMERIZATION;

EID: 77950026780     PISSN: 00476374     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mad.2010.01.009     Document Type: Article

References (27)

1. Bosgraaf L., Van Haastert P.J. Roc, a Ras/GTPase domain in complex proteins. Biochim. Biophys. Acta 2003, 1643:5-10.
2. Dachsel J.C., Mata I.F., Ross O.A., Taylor J.P., Lincoln S.J., Hinkle K.M., Huerta C., Ribacoba R., Blazquez M., Alvarez V., Farrer M.J. Digenic parkinsonism: investigation of the synergistic effects of PRKN and LRRK2. Neurosci. Lett. 2006, 410:80-84.
3. Dachsel J.C., Taylor J.P., Mok S.S., Ross O.A., Hinkle K.M., Bailey R.M., Hines J.H., Szutu J., Madden B., Petrucelli L., Farrer M.J. Identification of potential protein interactors of Lrrk2. Parkinsonism Relat. Disord. 2007, 13:382-385.
4. Gillardon F. Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability-a point of convergence in Parkinsonian neurodegeneration?. J. Neurochem. 2009.
5. Gillardon F. Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro. Neuroscience 2009.
6. Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet. 2006, 15:223-232.
7. Greggio E., Lewis P.A., van der Brug M.P., Ahmad R., Kaganovich A., Ding J., Beilina A., Baker A.K., Cookson M.R. Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. J. Neurochem. 2007, 102:93-102.
8. Greggio E., Zambrano I., Kaganovich A., Beilina A., Taymans J.M., Daniels V., Lewis P., Jain S., Ding J., Syed A., Thomas K.J., Baekelandt V., Cookson M.R. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J. Biol. Chem. 2008, 283:16906-16914.
9. Greggio E., Taymans J.M., Zhen E.Y., Ryder J., Vancraenenbroeck R., Beilina A., Sun P., Deng J., Jaffe H., Baekelandt V., Merchant K., Cookson M.R. The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites. Biochem. Biophys. Res. Commun. 2009, 389:449-454.
10. Haugarvoll K., Toft M., Ross O.A., White L.R., Aasly J.O., Farrer M.J. Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway. Neurosci. Lett. 2007, 416:299-301.
11. Haugarvoll K., Rademakers R., Kachergus J.M., Nuytemans K., Ross O.A., Gibson J.M., Tan E.K., Gaig C., Tolosa E., Goldwurm S., Guidi M., Riboldazzi G., Brown L., Walter U., Benecke R., Berg D., Gasser T., Theuns J., Pals P., Cras P., De Deyn P.P., Engelborghs S., Pickut B., Uitti R.J., Foroud T., Nichols W.C., Hagenah J., Klein C., Samii A., Zabetian C.P., Bonifati V., Van Broeckhoven C., Farrer M.J., Wszolek Z.K. Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. Neurology 2008, 70:1456-1460.
12. Healy D.G., Falchi M., O'Sullivan S.S., Bonifati V., Durr A., Bressman S., Brice A., Aasly J., Zabetian C.P., Goldwurm S., Ferreira J.J., Tolosa E., Kay D.M., Klein C., Williams D.R., Marras C., Lang A.E., Wszolek Z.K., Berciano J., Schapira A.H., Lynch T., Bhatia K.P., Gasser T., Lees A.J., Wood N.W. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol. 2008, 7:583-590.
13. Hughes A.J., Ben-Shlomo Y., Daniel S.E., Lees A.J. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. Neurology 1992, 42:1142-1146.
14. Hulihan M.M., Ishihara-Paul L., Kachergus J., Warren L., Amouri R., Elango R., Prinjha R.K., Upmanyu R., Kefi M., Zouari M., Sassi S.B., Yahmed S.B., El Euch-Fayeche G., Matthews P.M., Middleton L.T., Gibson R.A., Hentati F., Farrer M.J. LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol. 2008, 7:591-594.
15. Ishihara L., Gibson R.A., Warren L., Amouri R., Lyons K., Wielinski C., Hunter C., Swartz J.E., Elango R., Akkari P.A., Leppert D., Surh L., Reeves K.H., Thomas S., Ragone L., Hattori N., Pahwa R., Jankovic J., Nance M., Freeman A., Gouider-Khouja N., Kefi M., Zouari M., Ben Sassi S., Ben Yahmed S., El Euch-Fayeche G., Middleton L., Burn D.J., Watts R.L., Hentati F. Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families. Mov. Disord. 2007, 22:55-61.
16. Kaltenbach L.S., Romero E., Becklin R.R., Chettier R., Bell R., Phansalkar A., Strand A., Torcassi C., Savage J., Hurlburt A., Cha G.H., Ukani L., Chepanoske C.L., Zhen Y., Sahasrabudhe S., Olson J., Kurschner C., Ellerby L.M., Peltier J.M., Botas J., Hughes R.E. Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet. 2007, 3:e82.
17. Korr D., Toschi L., Donner P., Pohlenz H.D., Kreft B., Weiss B. LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain. Cell Signal. 2006, 18:910-920.
18. Li B., Leal S.M. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am. J. Hum. Genet. 2008, 83:311-321.
19. Marin I., van Egmond W.N., van Haastert P.J. The Roco protein family: a functional perspective. Faseb J. 2008, 22:3103-3110.
20. Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T., Hulihan M.M., Cobb S.A., Wu R.M., Lu C.S., Lahoz C., Wszolek Z.K., Farrer M.J. Lrrk2 pathogenic substitutions in Parkinson's disease. Neurogenetics 2005, 6:171-177.
21. Schaid D.J., Rowland C.M., Tines D.E., Jacobson R.M., Poland G.A. Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am. J. Hum. Genet. 2002, 70:425-434.
22. Sen S., Webber P.J., West A.B. Leucine-rich repeat kinase 2 (LRRK2) kinase activity: dependence on dimerization. J. Biol. Chem. 2009.
23. Shin N., Jeong H., Kwon J., Heo H.Y., Kwon J.J., Yun H.J., Kim C.H., Han B.S., Tong Y., Shen J., Hatano T., Hattori N., Kim K.S., Chang S., Seol W. LRRK2 regulates synaptic vesicle endocytosis. Exp. Cell Res. 2008, 314:2055-2065.
24. Taylor J.P., Hulihan M.M., Kachergus J.M., Melrose H.L., Lincoln S.J., Hinkle K.M., Stone J.T., Ross O.A., Hauser R., Aasly J., Gasser T., Payami H., Wszolek Z.K., Farrer M.J. Leucine-rich repeat kinase 1: a paralog of LRRK2 and a candidate gene for Parkinson's disease. Neurogenetics 2007, 8:95-102.
25. Wang L., Xie C., Greggio E., Parisiadou L., Shim H., Sun L., Chandran J., Lin X., Lai C., Yang W.J., Moore D.J., Dawson T.M., Dawson V.L., Chiosis G., Cookson M.R., Cai H. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J. Neurosci. 2008, 28:3384-3391.
26. Westerlund M., Belin A.C., Anvret A., Bickford P., Olson L., Galter D. Developmental regulation of leucine-rich repeat kinase 1 and 2 expression in the brain and other rodent and human organs: implications for Parkinson's disease. Neuroscience 2008, 152:429-436.
27. Zheng X.Y., Yang M., Tan J.Q., Pan Q., Long Z.G., Dai H.P., Xia K., Xia J.H., Zhang Z.H. Screening of LRRK2 interactants by yeast 2-hybrid analysis. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008, 33:883-891.