UMMS Affiliation

Department of Neurology

Publication Date


Document Type



Molecular and Cellular Neuroscience | Nervous System Diseases


Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3epsilon. Primary fibroblasts obtained from an E193K carrier demonstrated increased cellular toxicity and abnormal mitochondrial fission upon 1-methyl-4-phenylpyridinium treatment. We found that E193K alters LRRK2 binding to DRP1, a crucial mediator of mitochondrial fission. Our data support a role for LRRK2 as a scaffolding protein influencing mitochondrial fission.


DRP1, LRRK2, Parkinson’s disease, mitochondria, protein interaction

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Copyright © 2018 Perez Carrion, Pischedda, Biosa, Russo, Straniero, Civiero, Guida, Gloeckner, Ticozzi, Tiloca, Mariani, Pezzoli, Duga, Pichler, Pan, Landers, Greggio, Hess, Goldwurm and Piccoli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version



Front Mol Neurosci. 2018 Feb 28;11:64. doi: 10.3389/fnmol.2018.00064. eCollection 2018. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in molecular neuroscience


Full author list omitted for brevity. For the full list of authors, see article.

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PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.