Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of familial PD (Parkinson’s disease). Mutations that cause PD are found in either the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR [C-terminus of ROC (Ras of complex proteins)] domain. As well as the two catalytic domains, LRRK2 possesses several protein–protein interaction domains, but their function and the proteins with which they interact are poorly understood. In this issue of the Biochemical Journal, Nichols et al. study the interaction of the N-terminal region of LRRK2 with 14-3-3 proteins, regulatory proteins that often bind to phosphorylated regions of components of cell signalling pathways. Using a combination of techniques, Nichols et al. have identified two residues (Ser910 and Ser935) that are critically responsible for 14-3-3 binding. The interaction of LRRK2 with 14-3-3 proteins can prevent dephosphorylation of Ser910/Ser935 and stabilize LRRK2 structure, perhaps by influencing the dimerization of LRRK2. The ability to interact with 14-3-3 correlates with the pattern of intracellular LRRK2 distribution. Collectively, these new results identify a potentially important regulatory mechanism of this complex protein and might provide ways to think about therapeutic opportunities for PD.
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September 2010
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Commentary|
August 27 2010
14-3-3 proteins are promising LRRK2 interactors
Iakov N. Rudenko;
Iakov N. Rudenko
1Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20982-3707, U.S.A.
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Mark R. Cookson
Mark R. Cookson
1
1Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20982-3707, U.S.A.
1To whom correspondence should be addressed (email cookson@mail.nih.gov).
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Publisher: Portland Press Ltd
Received:
August 03 2010
Accepted:
August 04 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 430 (3): e5–e6.
Article history
Received:
August 03 2010
Accepted:
August 04 2010
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Citation
Iakov N. Rudenko, Mark R. Cookson; 14-3-3 proteins are promising LRRK2 interactors. Biochem J 15 September 2010; 430 (3): e5–e6. doi: https://doi.org/10.1042/BJ20101200
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