Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene have been identified in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's disease, although the biochemical properties of LRRK2 are not fully understood. It has been proposed that LRRK2 predominantly exists as a homodimer on the basis of the observation that LRRK2, with a theoretical molecular mass of 280 kDa, migrates at 600 kDa (p600 LRRK2) on native polyacrylamide gels. In the present study, we biochemically re-examined the nature of p600 LRRK2 and found that p600 LRRK2 was fractionated with a single peak at ~272 kDa by ultracentrifugation on a glycerol gradient. In addition, p600 LRRK2 behaved similarly to monomeric proteins upon two-dimensional electrophoretic separation. These results suggested a monomeric composition of p600 LRRK2 within cells. The p600 LRRK2 exhibited kinase activity as well as GTP-binding activity, and forced dimerization of LRRK2 neither upregulated its kinase activity nor altered its subcellular localization. Collectively, we conclude that the monomer form of LRRK2 is predominant within cells, and that dimerization is dispensable for its enzymatic activity.
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Research Article|
January 16 2012
Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form
Genta Ito;
Genta Ito
1Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan
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Takeshi Iwatsubo
Takeshi Iwatsubo
1
1Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan
1To whom correspondence should be addressed (email iwatsubo@m.u-tokyo.ac.jp).
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Publisher: Portland Press Ltd
Received:
July 07 2011
Revision Received:
October 07 2011
Accepted:
November 02 2011
Accepted Manuscript online:
November 02 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (3): 987–998.
Article history
Received:
July 07 2011
Revision Received:
October 07 2011
Accepted:
November 02 2011
Accepted Manuscript online:
November 02 2011
Citation
Genta Ito, Takeshi Iwatsubo; Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form. Biochem J 1 February 2012; 441 (3): 987–998. doi: https://doi.org/10.1042/BJ20111215
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