LRRK2 decreases microglial actin dynamics by filamentous actin depolymerization and Rac1 inhibition

References

• Chan D, Citro A, Cordy JM, Shen GC, Wolozin B. 2011. Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2). J Biol Chem. 6(286):16140–16149. Epub 20110316.
   Google Scholar
• Choi I, Kim B, Byun JW, Baik SH, Huh YH, Kim JH, Mook-Jung I, Song WK, Shin JH, Seo H, et al. 2015. LRRK2 g2019s mutation attenuates microglial motility by inhibiting focal adhesion kinase. Nat Commun. 14(6):8255. Epub 20150914.
   Google Scholar
• Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 8:752–758. Epub 20050515.
   PubMed Web of Science ®Google Scholar
• Dawson TM, Golde TE, Lagier-Tourenne C. 2018. Animal models of neurodegenerative diseases. Nat Neurosci. 21:1370–1379. Epub 20180924.
   PubMed Web of Science ®Google Scholar
• Eichhoff G, Brawek B, Garaschuk O. 2011. Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1813:1014–1024. Epub 20101105.
   PubMed Web of Science ®Google Scholar
• Gao HM, Hong JS. 2011. Gene-environment interactions: key to unraveling the mystery of Parkinson's disease. Prog Neurobiol. 94:1–19. Epub 20110323.
   PubMed Web of Science ®Google Scholar
• Gillardon F, Schmid R, Draheim H. 2012. Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience. 208:41–48. Epub 20120207.
   PubMed Web of Science ®Google Scholar
• Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D. 2006. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 9:1512–1519. Epub 20061119.
   PubMed Web of Science ®Google Scholar
• Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S, et al. 2008. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. The Lancet Neurology. 7:583–590. Epub 20080606.
   PubMed Web of Science ®Google Scholar
• Heppner FL, Skutella T, Hailer NP, Haas D, Nitsch R. 1998. Activated microglial cells migrate towards sites of excitotoxic neuronal injury inside organotypic hippocampal slice cultures. Eur J Neurosci. 10:3284–3290.
   PubMed Web of Science ®Google Scholar
• Ho DH, Lee H, Son I, Seol W. 2019. G2019s LRRK2 promotes mitochondrial fission and increases TNFα-mediated neuroinflammation responses. Animal Cells Syst (Seoul). 23:106–111. Epub 20190301.
   PubMed Web of Science ®Google Scholar
• Honda S, Sasaki Y, Ohsawa K, Imai Y, Nakamura Y, Inoue K, Kohsaka S. 2001. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J Neurosci. 21:1975–1982.
   PubMed Web of Science ®Google Scholar
• International Parkinson Disease Genomics C, Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simon-Sanchez J, Schulte C, Lesage S, et al. 2011. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet. 377:641–649. Epub 20110201.
   PubMed Web of Science ®Google Scholar
• Jeon J, Kim D, Jeon TJ. 2021. Opposite functions of RapA and RapC in cell adhesion and migration in Dictyostelium. Animal Cells Syst (Seoul). 25(4):203–210.
   PubMed Web of Science ®Google Scholar
• Joe E, Choi D, An J, Eun J, Jou I, Park S. 2018. Astrocytes, microglia, and Parkinson’s disease. Exp Neurobiol. 27(2):77–87.
   PubMed Web of Science ®Google Scholar
• Kicka S, Shen Z, Annesley SJ, Fisher PR, Lee S, Briggs S, Firtel RA. 2011. The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton. Mol Biol Cell. 22:2198–2211. Epub 20110505.
   PubMed Web of Science ®Google Scholar
• Kim B, Jeong HK, Kim JH, Lee SY, Jou I, Joe EH. 2011. Uridine 5′-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6receptor. The Journal of Immunology. 186:3701–3709. Epub 20110211.
   PubMed Web of Science ®Google Scholar
• Kim B, Yang MS, Choi D, Kim JH, Kim HS, Seol W, Choi S, Jou I, Kim EY, Joe EH. 2012. Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One. 7:e34693. Epub 20120409.
   PubMed Web of Science ®Google Scholar
• Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM. 2000. Localized Rac activation dynamics visualized in living cells. Science. 290:333–337.
   PubMed Web of Science ®Google Scholar
• Lee H, James WS, Cowley SA. 2017. LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson's disease. Biochem Soc Trans. 45:131–139.
   PubMed Web of Science ®Google Scholar
• Li X, Patel JC, Wang J, Avshalumov MV, Nicholson C, Buxbaum JD, Elder GA, Rice ME, Yue Z. 2010. Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S. J Neurosci. 30:1788–1797.
   PubMed Web of Science ®Google Scholar
• Meixner A, Boldt K, Van Troys M, Askenazi M, Gloeckner CJ, Bauer M, Marto JA, Ampe C, Kinkl N, Ueffing M. 2011. A QUICK screen for Lrrk2 interaction partners–leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics. Mol Cell Proteomics. 10:M110 001172. Epub 20100927.
   PubMed Web of Science ®Google Scholar
• Moehle MS, Daher JP, Hull TD, Boddu R, Abdelmotilib HA, Mobley J, Kannarkat GT, Tansey MG, West AB. 2015. The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins. Hum Mol Genet. 24:4250–4267. Epub 20150429.
   PubMed Web of Science ®Google Scholar
• Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB. 2012. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci. 32:1602–1611.
   PubMed Web of Science ®Google Scholar
• Nam D, Kim A, Han SJ, Lee S, Park S, Seol W. 2021. Analysis of α-synuclein levels related to LRRK2 kinase activity: from substantia nigra to urine of patients with Parkinson’s disease. Animal Cells Syst (Seoul). 25(1):28–36.
   PubMed Web of Science ®Google Scholar
• Neary JT, Kang Y, Willoughby KA, Ellis EF. 2003. Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors. J Neurosci. 23:2348–2356.
   PubMed Web of Science ®Google Scholar
• Nimmerjahn A, Kirchhoff F, Helmchen F. 2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 308:1314–1318. Epub 20050414.
   PubMed Web of Science ®Google Scholar
• Parisiadou L, Xie C, Cho HJ, Lin X, Gu XL, Long CX, Lobbestael E, Baekelandt V, Taymans JM, Sun L, et al. 2009. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J Neurosci. 29:13971–13980.
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. 1992. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 70:401–410.
   PubMed Web of Science ®Google Scholar
• Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, Shen J. 2009. R1441c mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci USA. 106:14622–14627.
   PubMed Web of Science ®Google Scholar