LRRK2 is required for CD38-mediated NAADP-Ca²⁺ signaling and the downstream activation of TFEB (transcription factor EB) in immune cells

References

• Bonello F, D’Agostino M, Moscvin M, et al. CD38 as an immunotherapeutic target in multiple myeloma. Expert Opin Biol Ther. 2018;18(12):1209–1221.
   PubMed Web of Science ®Google Scholar
• Frerichs KA, Nagy NA, Lindenbergh PL, et al. CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical experience. Expert Rev Clin Immunol. 2018;14(3):197–206.
   PubMed Web of Science ®Google Scholar
• Chini EN, Chini CCS, Espindola Netto JM, et al. The pharmacology of CD38/NADase: an emerging target in cancer and diseases of aging. Trends Pharmacol Sci. 2018;39(4):424–436.
   PubMed Web of Science ®Google Scholar
• Lee HC. Structure and enzymatic functions of human CD38. Mol Med (Cambridge, MA). 2006 Nov-Dec;12(11–12):317–323.
   PubMed Web of Science ®Google Scholar
• Fang C, Li T, Li Y, et al. CD38 produces nicotinic acid adenosine dinucleotide phosphate in the lysosome. J Biol Chem. 2018 May 25;293(21):8151–8160.
   PubMed Web of Science ®Google Scholar
• Cosker F, Cheviron N, Yamasaki M, et al. The Ecto-enzyme CD38 is a nicotinic acid adenine dinucleotide phosphate (NAADP) synthase that couples receptor activation to Ca2+ mobilization from lysosomes in pancreatic acinar cells. J Biol Chem. 2010 December 3;285(49):38251–38259.
   PubMed Web of Science ®Google Scholar
• Graeff R, Liu Q, Kriksunov IA, et al. Acidic residues at the active sites of CD38 and ADP-ribosyl cyclase determine nicotinic acid adenine dinucleotide phosphate (NAADP) synthesis and hydrolysis activities. J Biol Chem. 2006 Sep 29;281(39):28951–28957.
   PubMed Web of Science ®Google Scholar
• Knowles H, Li Y, Perraud A-L. The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation [journal article]. Immunol Res. 2013 March 01;55(1):241–248.
   PubMed Web of Science ®Google Scholar
• Ogunbayo OA, Zhu Y, Rossi D, et al. Cyclic adenosine diphosphate ribose activates ryanodine receptors, whereas NAADP activates two-pore domain channels. J Biol Chem. 2011 Mar 18;286(11):9136–9140.
   PubMed Web of Science ®Google Scholar
• Calcraft PJ, Ruas M, Pan Z, et al. NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature. 2009;459(7246):596.
   PubMed Web of Science ®Google Scholar
• Pitt SJ, Funnell TM, Sitsapesan M, et al. TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. J Biol Chem. 2010 Nov 5;285(45):35039–35046.
   PubMed Web of Science ®Google Scholar
• Jiang H, Acharya C, An G, et al. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide. Leukemia. 2016 Feb;30(2):399–408.
   PubMed Web of Science ®Google Scholar
• Overdijk MB, Jansen JH, Nederend M, et al. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via fcgamma receptor-mediated cross-linking. J Immunol. 2016 Aug 1;197(3):807–813.
   PubMed Web of Science ®Google Scholar
• Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat Rev Neurosci. 2010;11(12):791–797.
   PubMed Web of Science ®Google Scholar
• Humphries F, Yang S, Wang B, et al. RIP kinases: key decision makers in cell death and innate immunity. Cell Death Differ. 2015 Feb;22(2):225–236.
   PubMed Web of Science ®Google Scholar
• Healy DG, Falchi M, O’Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 2008 7; Jul(7):583–590.
   Google Scholar
• Cookson MR. Cellular functions of LRRK2 implicate vesicular trafficking pathways in Parkinson’s disease. Biochem Soc Trans. 2016;44(6):1603–1610.
   PubMedGoogle Scholar
• Anderson CA, Boucher G, Lees CW, et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet. 2011 Mar;43(3):246–252.
   PubMed Web of Science ®Google Scholar
• Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008 Aug;40(8):955–962.
   PubMed Web of Science ®Google Scholar
• Waro BJ, Aasly JO. Exploring cancer in LRRK2 mutation carriers and idiopathic Parkinson’s disease. Brain Behav. 2018 Jan;8(1):e00858.
   PubMed Web of Science ®Google Scholar
• Gardet A, Benita Y, Li C, et al. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol. 2010 Nov 1;185(9):5577–5585.
   PubMed Web of Science ®Google Scholar
• Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity [Review]. Nat Rev Immunol. 2013;13(10):722–737.
   PubMed Web of Science ®Google Scholar
• Settembre C, Di Malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011 Jun 17;332(6036):1429–1433.
   PubMed Web of Science ®Google Scholar
• Nabar NR, Kehrl JH. The transcription Factor EB links cellular stress to the immune response. Yale J Biol Med. 2017 Jun;90(2):301–315.
   PubMed Web of Science ®Google Scholar
• Rah SY, Lee YH, Kim UH. NAADP-mediated Ca(2+) signaling promotes autophagy and protects against LPS-induced liver injury. Faseb J. 2017 Jul;31(7):3126–3137.
   PubMed Web of Science ®Google Scholar
• Bao JX, Zhang QF, Wang M, et al. Implication of CD38 gene in autophagic degradation of collagen I in mouse coronary arterial myocytes. Front Biosci (Landmark Ed). 2017 Jan 1;22:558–569.
   PubMed Web of Science ®Google Scholar
• Xiong J, Xia M, Xu M, et al. Autophagy maturation associated with CD38-mediated regulation of lysosome function in mouse glomerular podocytes. J Cell Mol Med. 2013;17(12):1598–1607.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Xu M, Xia M, et al. Defective autophagosome trafficking contributes to impaired autophagic flux in coronary arterial myocytes lacking CD38 gene. Cardiovasc Res. 2014;102(1):68–78.
   PubMed Web of Science ®Google Scholar
• Manzoni C. The LRRK2–macroautophagy axis and its relevance to Parkinson’s disease. Biochem Soc Trans. 2017;45(1):155.
   PubMedGoogle Scholar
• Schapansky J, Nardozzi JD, Felizia F, et al. Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum Mol Genet. 2014 Aug 15;23(16):4201–4214.
   PubMed Web of Science ®Google Scholar
• Gomez-Suaga P, Luzon-Toro B, Churamani D, et al. Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum Mol Genet. 2012 Feb 1;21(3):511–525.
   PubMed Web of Science ®Google Scholar
• Gomez-Suaga P, Churchill GC, Patel S, et al. A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium signalling. Biochem Soc Trans. 2012 Oct;40(5):1140–1146.
   PubMedGoogle Scholar
• Funaro A, Reinis M, Trubiani O, et al. CD38 functions are regulated through an internalization step. J Immunol. 1998 Mar 1;160(5):2238–2247.
   PubMed Web of Science ®Google Scholar
• ZOCCHI E, USAI C, GUIDA L, et al. Ligand-induced internalization of CD38 results in intracellular Ca2+ mobilization: role of NAD+ transport across cell membranes. FASEB J. 1999;13(2):273–283.
   PubMed Web of Science ®Google Scholar
• Medina DL, Di Paola S, Peluso I, et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB [Article]. Nat Cell Biol. 2015;17(3):288–299.
   PubMed Web of Science ®Google Scholar
• Gerasimenko JV, Charlesworth RM, Sherwood MW, et al. Both RyRs and TPCs are required for NAADP-induced intracellular Ca(2)(+) release. Cell Calcium. 2015 Sep;58(3):237–245.
   PubMed Web of Science ®Google Scholar
• Zhu MX, Evans AM, Ma J, et al. Two-pore channels for integrative Ca signaling. Commun Integr Biol. 2010 Jan-Feb;3(1):12–17.
   PubMedGoogle Scholar
• Yue M, Hinkle KM, Davies P, et al. Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol Dis. 2015 Jun;78:172–195.
   PubMed Web of Science ®Google Scholar
• Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife. 2016;5:e12813.
   PubMed Web of Science ®Google Scholar
• Dzamko N, Inesta-Vaquera F, Zhang J, et al. The IkappaB kinase family phosphorylates the Parkinson’s disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling. PLoS One. 2012;7(6):e39132.
   PubMed Web of Science ®Google Scholar
• Pastore N, Brady OA, Diab HI, et al. TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy. 2016;12(8):1240–1258.
   PubMed Web of Science ®Google Scholar
• Galván-Peña S, O’Neill LAJ. Metabolic reprograming in macrophage polarization. Front Immunol. 2014;5:420.
   PubMed Web of Science ®Google Scholar
• Tannahill GM, Curtis AM, Adamik J, et al. Succinate is a danger signal that induces IL-1β via HIF-1α. Nature. 2013;496(7444):238–242.
   PubMed Web of Science ®Google Scholar
• Chen D, Xie J, Fiskesund R, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun. 2018;9(1):873.
   PubMed Web of Science ®Google Scholar
• Van den Bossche J, Baardman J, de Winther MPJ. Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis. J. Vis. Exp. 2015;105:e53424. doi:https://doi.org/10.3791/53424.
   Google Scholar
• Hockey LN, Kilpatrick BS, Eden ER, et al. Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition. J Cell Sci. 2015 Jan 15;128(2):232–238.
   PubMed Web of Science ®Google Scholar
• Shin HJ, Kim H, Oh S, et al. AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy. Nature. 2016 Jun 15;534(7608):553–557.
   PubMed Web of Science ®Google Scholar
• Yasue T, Nishizumi H, Aizawa S, et al. A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5. Proc Natl Acad Sci U S A. 1997;94(19):10307–10312.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Alba JC, Moreno-Garcia ME, Sandoval-Montes C, et al. CD38 induces differentiation of immature transitional 2 B lymphocytes in the spleen. Blood. 2008 Apr 1;111(7):3644–3652.
   PubMed Web of Science ®Google Scholar
• Moreno-Garcia ME, Lopez-Bojorques LN, Zentella A, et al. CD38 signaling regulates B lymphocyte activation via a phospholipase C (PLC)-gamma 2-independent, protein kinase C, phosphatidylcholine-PLC, and phospholipase D-dependent signaling cascade. J Immunol. 2005 Mar 1;174(5):2687–2695.
   PubMed Web of Science ®Google Scholar
• Gul R, Park DR, Shawl AI, et al. Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-Ribose (cADPR) mediate Ca2+ signaling in cardiac hypertrophy induced by β-adrenergic stimulation. PLoS One. 2016;11(3):e0149125.
   PubMed Web of Science ®Google Scholar
• Soares S, Thompson M, White T, et al. NAADP as a second messenger: neither CD38 nor base-exchange reaction are necessary for in vivo generation of NAADP in myometrial cells. Am J Physiol Cell Physiol. 2007 Jan;292(1):C227–39.
   PubMed Web of Science ®Google Scholar
• Moreschi I, Bruzzone S, Melone L, et al. NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases. Biochem Biophys Res Commun. 2006 Jun 30;345(2):573–580.
   PubMed Web of Science ®Google Scholar
• Lin WK, Bolton EL, Cortopassi WA, et al. Synthesis of the Ca(2+)-mobilizing messengers NAADP and cADPR by intracellular CD38 enzyme in the mouse heart: role in β-adrenoceptor signaling. J Biol Chem. 2017 Aug 11;292(32):13243–13257.
   PubMed Web of Science ®Google Scholar
• Park DR, Nam TS, Kim YW, et al. Oxidative activation of type III CD38 by NADPH oxidase-derived hydrogen peroxide in Ca(2+) signaling. Faseb J. 2018 Nov 19;33(3):3404-3419.fj201800235R.
   Google Scholar
• Gómez-Suaga P, Rivero-Ríos P, Fdez E, et al. LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity. Hum Mol Genet. 2014 Dec 20;23(25):6779–6796.
   PubMed Web of Science ®Google Scholar
• Rivero-Ríos P, Romo-Lozano M, Madero-Pérez J, et al. The G2019S variant of leucine-rich repeat kinase 2 (LRRK2) alters endolysosomal trafficking by impairing the function of the GTPase RAB8A. J Biol Chem. 2019 Mar 29;294(13):4738–4758.
   PubMed Web of Science ®Google Scholar
• Amici SA, Young NA, Narvaez-Miranda J, et al. CD38 is robustly induced in human macrophages and monocytes in inflammatory conditions [Original Research]. Front Immunol. 2018 Jul 10;9(1593). DOI:https://doi.org/10.3389/fimmu.2018.01593
   Google Scholar
• Kang J, Park KH, Kim JJ, et al. The role of CD38 in Fcgamma receptor (FcgammaR)-mediated phagocytosis in murine macrophages. J Biol Chem. 2012 Apr 27;287(18):14502–14514.
   PubMed Web of Science ®Google Scholar
• Shu B, Feng Y, Gui Y, et al. Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-κB signaling suppression. Cell Signal. 2018;42:249–258.
   PubMed Web of Science ®Google Scholar
• Viegas MS, do Carmo A, Silva T, et al. CD38 plays a role in effective containment of mycobacteria within granulomata and polarization of Th1 immune responses against Mycobacterium avium. Microbes Infect. 2007 Jun;9(7):847–854.
   PubMed Web of Science ®Google Scholar
• Lischke T, Heesch K, Schumacher V, et al. CD38 controls the innate immune response against Listeria monocytogenes. Infect Immun. 2013;81(11):4091.
   PubMed Web of Science ®Google Scholar
• Liu W, Liu X, Li Y, et al. LRRK2 promotes the activation of NLRC4 inflammasome during Salmonella Typhimurium infection. J Exp Med. 2017;214(10):3051.
   PubMed Web of Science ®Google Scholar
• Lin X, Parisiadou L, Gu X-L, et al. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson’s-disease-related mutant α-synuclein. Neuron. 2009;64(6):807–827.
   PubMed Web of Science ®Google Scholar
• Vural A, Nabar NR, Hwang IY, et al. Gα i2 signaling regulates inflammasome priming and cytokine production by biasing macrophage phenotype determination. J Immunol. 2019 Jan 25;202:1510–1520.
   PubMed Web of Science ®Google Scholar
• Greggio E, Zambrano I, Kaganovich A, et al. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J Biol Chem. 2008 Jun 13;283(24):16906–16914.
   PubMed Web of Science ®Google Scholar
• Greggio E, Jain S, Kingsbury A, et al. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis. 2006;23(2):329–341.
   PubMed Web of Science ®Google Scholar
• Yue Y, Nabar NR, Shi CS, et al. SARS-coronavirus open reading Frame-3a drives multimodal necrotic cell death. Cell Death Dis. 2018 Sep 5;9(9):904.
   PubMedGoogle Scholar
• Ferron M, Settembre C, Shimazu J, et al. A RANKL-PKCbeta-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes Dev. 2013 Apr 15;27(8):955–969.
   PubMed Web of Science ®Google Scholar
• Chauhan S, Goodwin JG, Chauhan S, et al. ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell. 2013 Apr 11;50(1):16–28.
   PubMed Web of Science ®Google Scholar
• Chini CCS, Guerrico AMG, Nin V, et al. Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy for pancreatic tumors. Clin Cancer Res. 2014;20(1):120.
   PubMed Web of Science ®Google Scholar
• Wang C, Niederstrasser H, Douglas PM, et al. Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan. Nat Commun. 2017 Dec 22;8(1):2270.
   PubMedGoogle Scholar