In the period since LRRK2 (leucine-rich repeat kinase 2) was identified as a causal gene for late-onset autosomal dominant parkinsonism, a great deal of work has been aimed at understanding whether the LRRK2 protein might be a druggable target for Parkinson's disease (PD). As part of this effort, animal models have been developed to explore both the normal and the pathophysiological roles of LRRK2. However, LRRK2 is part of a wider family of proteins whose functions in different organisms remain poorly understood. In this review, we compare the information available on biochemical properties of LRRK2 homologues and orthologues from different species from invertebrates (e.g. Caenorhabditis elegans and Drosophila melanogaster) to mammals. We particularly discuss the mammalian LRRK2 homologue, LRRK1, and those species where there is only a single LRRK homologue, discussing examples where each of the LRRK family of proteins has distinct properties as well as those cases where there appear to be functional redundancy. We conclude that uncovering the function of LRRK2 orthologues will help to elucidate the key properties of human LRRK2 as well as to improve understanding of the suitability of different animal models for investigation of LRRK2-related PD.
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February 2016
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Point scanning confocal microscopic imaging of C2C12 undifferentiatedmyoblasts (top panels) and differentiatedmultinucleated myotubes (bottom panels) immunofluorescently labelled with DAPI (blue) PDLIM7 (green) and Phalloidin or Nedd4-1 (red). Merged images show co-localization of PDLIM7 and Phalloidin decreases with myotube formation (left panels) and co-location of PDLIM7 and Nedd4-1 increases with myotube formation (right panels). Image courtesy of Robert D’Cruz et al. (for further details see pages 267–276). - PDF Icon PDF LinkFront Matter
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Review Article|
January 25 2016
The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research
Rebekah G. Langston;
Rebekah G. Langston
*Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A.
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Iakov N. Rudenko;
Iakov N. Rudenko
1
*Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A.
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Mark R. Cookson
Mark R. Cookson
2
*Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD 20892, U.S.A.
2To whom correspondence should be addressed (email cookson@mail.nih.gov).
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Publisher: Portland Press Ltd
Received:
September 10 2015
Revision Received:
November 10 2015
Accepted:
November 25 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (3): 221–232.
Article history
Received:
September 10 2015
Revision Received:
November 10 2015
Accepted:
November 25 2015
Citation
Rebekah G. Langston, Iakov N. Rudenko, Mark R. Cookson; The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. Biochem J 1 February 2016; 473 (3): 221–232. doi: https://doi.org/10.1042/BJ20150985
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