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http://dx.doi.org/10.15616/BSL.2020.26.1.47

The Physical Interaction between Nucleotide-Binding Oligomerization Domain Containing 2 and Leucine-Rich Repeat Kinase 2  

Jung, Ji-A (Department of Biomedical Laboratory Science, College of Health and Nursing, Kyungwoon University)
Park, Sangwook (Department of Biomedical Laboratory Science, College of Health and Nursing, Kyungwoon University)
Abstract
Recently, decades of robust researches on degenerative brain disorder have been highlighted on the interactive connection of gut and brain. In terms of inflammatory cytokine production, others have shown that Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) is involved with Leucine-Rich Repeat Kinase 2 (LRRK2). HEK293T cells were transiently co-transfected with Myc-tagged LRRK2 and Flag-tagged NOD2 and then followed by co-immunoprecipitation assay. In this study, we provide the novel finding of physical protein-protein interaction between NOD2 and LRRK2. G2019S variant has shown stronger interactions against NOD2 than those of wild type LRRK2. In an axis of NOD2-LRRK2 communication, it is believed to pave a new way in the understanding of the bidirectional molecular mechanism of brain disorder, including Parkinson's disease into gut inflammatory disease, including Crohn's disease.
Keywords
NOD2; Crohn's disease; LRRK2; Parkinson's disease; Protein-protein interaction;
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1 Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, Vavricka SR, Fiocchi C. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastro Hepat. 2018. 15: 39.   DOI
2 Cryan JF, Dinan TG. Gut microbiota: Microbiota and neuroimmune signalling-Metchnikoff to microglia. Nat Rev Gastro Hepat. 2015. 12: 494-496.   DOI
3 Cummings JL. Depression and Parkinson's disease: a review. Am J of Psychiatry. 1992. 149: 443-454.   DOI
4 Gareau MG. Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol. 2014. 817: 357-371.   DOI
5 Park S, Ha SD, Coleman M, Meshkibaf S, Kim SO. p62/SQSTM1 enhances NOD2-mediated signaling and cytokine production through stabilizing NOD2 oligomerization. PLoS One. 2013. 8: e57138.   DOI
6 Park S, Han S, Choi I, Kim B, Park SP, Joe EH, Suh YH. Interplay between Leucine-Rich Repeat Kinase 2 (LRRK2) and p62/SQSTM-1 in Selective Autophagy. PLoS One. 2016. 11: e0163029.   DOI
7 Rajput A, Dickson DW, Robinson CA, Ross OA, Daechsel JC, Lincoln SJ, Cobb SA, Rajput ML, Farrer MJ. Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurol. 2006. 67: 1506-1508.   DOI
8 Rocha JD, Schlossmacher MG, Philpott DJ. LRRK2 and Nod2 promote lysozyme sorting in Paneth cells. Nat Immunol. 2015. 16: 898-900.   DOI
9 Van Limbergen J, Wilson DC, Satsangi J. The genetics of Crohn's disease. Annu Rev Genom Hum Genet. 2009. 10: 89-116.   DOI
10 Yan R, Liu Z. LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation. Protein Cell. 2017. 8: 55-66.   DOI