Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells.
Apoptosis
Cell Line
Cell Membrane
/ metabolism
Exocytosis
Glyceraldehyde-3-Phosphate Dehydrogenases
/ metabolism
Humans
Lipopolysaccharide Receptors
/ metabolism
Lysosomes
/ metabolism
Phagocytes
/ metabolism
Phagocytosis
Phosphatidylserines
/ metabolism
Phospholipid Transfer Proteins
/ metabolism
Protein Binding
Protein Isoforms
/ metabolism
Stress, Physiological
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
30 09 2021
30 09 2021
Historique:
received:
06
04
2021
accepted:
15
09
2021
revised:
02
09
2021
entrez:
1
10
2021
pubmed:
2
10
2021
medline:
4
2
2022
Statut:
epublish
Résumé
Rapid clearance of apoptotic cells by phagocytes is crucial for organogenesis, tissue homeostasis, and resolution of inflammation. This process is initiated by surface exposure of various 'eat me' ligands. Though phosphatidylserine (PS) is the best recognized general recognition ligand till date, recent studies have shown that PS by itself is not sufficient for clearance of apoptotic cells. In this study, we have identified a specific pleioform of GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) that functions as an 'eat me' signal on apoptotic cell surface. This specific form of GAPDH which is exposed on surface of apoptotic cells was found to interact with CD14 present on plasma membrane of phagocytes leading to their engulfment. This is the first study demonstrating the novel interaction between multifunctional GAPDH and the phagocytic receptor CD14 resulting in apoptotic cell clearance (efferocytosis).
Identifiants
pubmed: 34593755
doi: 10.1038/s41419-021-04168-8
pii: 10.1038/s41419-021-04168-8
pmc: PMC8482365
doi:
Substances chimiques
Lipopolysaccharide Receptors
0
Phosphatidylserines
0
Phospholipid Transfer Proteins
0
Protein Isoforms
0
Glyceraldehyde-3-Phosphate Dehydrogenases
EC 1.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
892Informations de copyright
© 2021. The Author(s).
Références
Green DR, Ferguson T, Zitvogel L, Kroemer G. Immunogenic and tolerogenic cell death. Nat Rev Immunol. 2009;9:353–63.
pubmed: 19365408
pmcid: 2818721
doi: 10.1038/nri2545
Ren Y, Tang J, Mok M, Chan AW, Wu A, Lau C. Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus. Arthritis Rheumatol. 2003;48:2888–97.
doi: 10.1002/art.11237
Nagata S, Hanayama R, Kawane K. Autoimmunity and the clearance of dead cells. Cell 2010;140:619–30.
pubmed: 20211132
doi: 10.1016/j.cell.2010.02.014
Schrijvers DM, De Meyer GR, Kockx MM, Herman AG, Martinet W. Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25:1256–61.
pubmed: 15831805
doi: 10.1161/01.ATV.0000166517.18801.a7
Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:282–86.
pubmed: 19741708
pmcid: 2851546
doi: 10.1038/nature08296
Truman LA, Ford CA, Pasikowska M, Pound JD, Wilkinson SJ, Dumitriu IE, et al. CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 2008;112:5026–36.
pubmed: 18799722
doi: 10.1182/blood-2008-06-162404
Birge R, Boeltz S, Kumar S, Carlson J, Wanderley J, Calianese D, et al. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death Differ. 2016;23:962–78.
pubmed: 26915293
pmcid: 4987730
doi: 10.1038/cdd.2016.11
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005;123:321–34.
pubmed: 16239148
doi: 10.1016/j.cell.2005.08.032
Clarke C, Smyth MJ. Calreticulin exposure increases cancer immunogenicity. Nat Biotechnol. 2007;25:192–93.
pubmed: 17287754
doi: 10.1038/nbt0207-192
Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol. 2014;14:166–80.
pubmed: 24481336
pmcid: 4040260
doi: 10.1038/nri3607
Szondy Z, Garabuczi É, Joós G, Tsay GJ, Sarang Z. Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. Front Immunol. 2014;5:354.
pubmed: 25136342
pmcid: 4117929
doi: 10.3389/fimmu.2014.00354
Segawa K, Suzuki J, Nagata S. Constitutive exposure of phosphatidylserine on viable cells. Proc Natl Acad Sci. 2011;108:19246–51.
pubmed: 22084121
pmcid: 3228483
doi: 10.1073/pnas.1114799108
Ucker DS, Jain MR, Pattabiraman G, Palasiewicz K, Birge RB, Li H. Externalized glycolytic enzymes are novel, conserved, and early biomarkers of apoptosis. J Biol Chem. 2012;287:10325–43.
pubmed: 22262862
pmcid: 3323007
doi: 10.1074/jbc.M111.314971
Tristan C, Shahani N, Sedlak TW, Sawa A. The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal. 2011;23:317–23.
pubmed: 20727968
doi: 10.1016/j.cellsig.2010.08.003
Hwang S, Disatnik MH, Mochly‐Rosen D. Impaired GAPDH‐induced mitophagy contributes to the pathology of Huntington’s disease. EMBO Mol Med. 2015;7:1307–26.
pubmed: 26268247
pmcid: 4604685
doi: 10.15252/emmm.201505256
Sheokand N, Malhotra H, Kumar S, Tillu VA, Chauhan AS, Raje CI, et al. Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells. J Cell Sci. 2014;127:4279–91.
pubmed: 25074810
Seidler NW. GAPDH: biological properties and diversity. Springer Science & Business Media; 2012.
Rawat P, Kumar S, Sheokand N, Raje CI, Raje M. The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor. Biochem Cell Biol. 2012;90:329–38.
pubmed: 22292499
doi: 10.1139/o11-058
Kumar S, Sheokand N, Mhadeshwar MA, Raje CI, Raje M. Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor. Int J Biochem Cell Biol. 2012;44:189–99.
pubmed: 22062951
doi: 10.1016/j.biocel.2011.10.016
Glaser PE, Gross RW. Rapid plasmenylethanolamine-selective fusion of membrane bilayers catalyzed by an isoform of glyceraldehyde-3-phosphate dehydrogenase: discrimination between glycolytic and fusogenic roles of individual isoforms. Biochemistry 1995;34:12193–203.
pubmed: 7547960
doi: 10.1021/bi00038a013
Polati R, Castagna A, Bossi AM, Alberio T, De Domenico I, Kaplan J, et al. Murine macrophages response to iron. J Proteom. 2012;76:10–27.
doi: 10.1016/j.jprot.2012.07.018
Chauhan AS, Kumar M, Chaudhary S, Dhiman A, Patidar A, Jakhar P, et al. Trafficking of a multifunctional protein by endosomal microautophagy: linking two independent unconventional secretory pathways. FASEB J. 2019;33:5626–40.
pubmed: 30640524
doi: 10.1096/fj.201802102R
Fadeel B, Xue D. The ins and outs of phospholipid asymmetry in the plasma membrane: roles in health and disease. Crit Rev Biochem Mol Biol. 2009;44:264–77.
pubmed: 19780638
pmcid: 2787517
doi: 10.1080/10409230903193307
Kaneda M, Takeuchi K-I, Inoue K, Umeda M. Localization of the phosphatidylserine-binding site of glyceraldehyde-3-phosphate dehydrogenase responsible for membrane fusion. J Biochem. 1997;122:1233–40.
pubmed: 9498570
doi: 10.1093/oxfordjournals.jbchem.a021886
Azab W, Gramatica A, Herrmann A, Osterrieder N. Binding of alphaherpesvirus glycoprotein H to surface α4β1-integrins activates calcium-signaling pathways and induces phosphatidylserine exposure on the plasma membrane. MBio 2015;6:e01552–15.
pubmed: 26489864
pmcid: 4620472
doi: 10.1128/mBio.01552-15
Wesseling MC, Wagner-Britz L, Nguyen DB, Asanidze S, Mutua J, Mohamed N, et al. Novel insights in the regulation of phosphatidylserine exposure in human red blood cells. Cell Physiol Biochem. 2016;39:1941–54.
pubmed: 27771709
doi: 10.1159/000447891
Devitt A, Parker KG, Ogden CA, Oldreive C, Clay MF, Melville LA, et al. Persistence of apoptotic cells without autoimmune disease or inflammation in CD14−/− mice. J Cell Biol 2004;167:1161–70.
pubmed: 15611337
pmcid: 2172617
doi: 10.1083/jcb.200410057
Thomas L, Bielemeier A, Lambert PA, Darveau RP, Marshall LJ, Devitt A. The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells. PLoS ONE. 2013;8:e70691.
pubmed: 23936239
pmcid: 3728300
doi: 10.1371/journal.pone.0070691
Guillou C, Fréret M, Fondard E, Derambure C, Avenel G, Golinski M-L, et al. Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function. Sci Rep. 2016;6:23796.
pubmed: 27025255
pmcid: 4824496
doi: 10.1038/srep23796
Boada-Romero E, Martinez J, Heckmann BL, Green DR. The clearance of dead cells by efferocytosis. Nat Rev Mol Cell Biol. 2020;21:398–414.
pubmed: 32251387
pmcid: 7392086
doi: 10.1038/s41580-020-0232-1
Ravichandran KS. Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 2010;207:1807–17.
pubmed: 20805564
pmcid: 2931173
doi: 10.1084/jem.20101157
Li W. Eat-me signals: keys to molecular phagocyte biology and “appetite” control. J Cell Physiol 2012;227:1291–7.
pubmed: 21520079
pmcid: 3242927
doi: 10.1002/jcp.22815
Park S-Y, Kim I-S. Engulfment signals and the phagocytic machinery for apoptotic cell clearance. Exp Mol Med. 2017;49:e331–e. 2017/05/01
pubmed: 28496201
pmcid: 5454446
doi: 10.1038/emm.2017.52
Raje CI, Kumar S, Harle A, Nanda JS, Raje M. The macrophage cell surface glyceraldehyde-3-phosphate dehydrogenase is a novel transferrin receptor. J Biol Chem. 2007;282:3252–61.
pubmed: 17121833
doi: 10.1074/jbc.M608328200
Sheokand N, Malhotra H, Chauhan AS, Kumar M, Chaudhary S, Patidar A, et al. Reverse overshot water-wheel retroendocytosis of apotransferrin extrudes cellular iron. J cell Sci. 2016;129:843–53.
pubmed: 26743084
Terrasse R, Tacnet-Delorme P, Moriscot C, Pérard J, Schoehn G, Vernet T, et al. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein. J Biol Chem. 2012;287:42620–33.
pubmed: 23086952
pmcid: 3522263
doi: 10.1074/jbc.M112.423731
Yang H, Zubarev RA. Mass spectrometric analysis of asparagine deamidation and aspartate isomerization in polypeptides. Electrophoresis 2010;31:1764–72.
pubmed: 20446295
pmcid: 3104603
doi: 10.1002/elps.201000027
Madian AG, Hindupur J, Hulleman JD, Diaz-Maldonado N, Mishra VR, Guigard E, et al. Effect of single amino acid substitution on oxidative modifications of the Parkinson’s disease-related protein, DJ-1. Mol Cell Proteom. 2012;11:M111. 010892
doi: 10.1074/mcp.M111.010892
Bond ST, Howlett KF, Kowalski GM, Mason S, Connor T, Cooper A, et al. Lysine post-translational modification of glyceraldehyde-3-phosphate dehydrogenase regulates hepatic and systemic metabolism. FASEB J. 2017;31:2592–602.
pubmed: 28258188
doi: 10.1096/fj.201601215R
Knorre D, Kudryashova N, Godovikova T. Chemical and functional aspects of posttranslational modification of proteins. Acta Naturae. 2009;1:29–51.
pubmed: 22649613
pmcid: 3347534
doi: 10.32607/20758251-2009-1-3-29-51
Lee S. Post-translational modification of proteins in toxicological research: focus on lysine acylation. Toxicological Res. 2013;29:81–86.
doi: 10.5487/TR.2013.29.2.081
Resh MD. Covalent lipid modifications of proteins. Curr Biol. 2013;23:R431–R5.
pubmed: 23701681
pmcid: 3712495
doi: 10.1016/j.cub.2013.04.024
Xu H, Chen X, Xu X, Shi R, Suo S, Cheng K, et al. Lysine acetylation and succinylation in HeLa cells and their essential roles in response to UV-induced stress. Sci Rep. 2016;6:30212.
pubmed: 27452117
pmcid: 4959001
doi: 10.1038/srep30212
Zha J, Weiler S, Oh KJ, Wei MC, Korsmeyer SJ. Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science 2000;290:1761–5.
pubmed: 11099414
doi: 10.1126/science.290.5497.1761
de Jonge HR, Hogema B, Tilly BC. Protein N-myristoylation: critical role in apoptosis and salt tolerance. Sci Signal. 2000;2000:pe1–pe.
doi: 10.1126/stke.2000.63.pe1
Deverman BE, Cook BL, Manson SR, Niederhoff RA, Langer EM, Rosová I, et al. Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage. Cell 2002;111:51–62.
pubmed: 12372300
doi: 10.1016/S0092-8674(02)00972-8
Park S-S, Gonzalez-Juarbe N, Riegler AN, Im H, Hale Y, Platt MP, et al. Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza. Cell Rep. 2021;35:109267.
pubmed: 34133917
pmcid: 8265312
doi: 10.1016/j.celrep.2021.109267
Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, et al. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell 2011;147:868–80.
pubmed: 22078883
pmcid: 3217211
doi: 10.1016/j.cell.2011.09.051
Devitt A, Pierce S, Oldreive C, Shingler W, Gregory C. CD14-dependent clearance of apoptotic cells by human macrophages: the role of phosphatidylserine. Cell death Differ. 2003;10:371.
pubmed: 12700637
doi: 10.1038/sj.cdd.4401168
Schlegel RA, Krahling S, Callahan MK, Williamson P. CD14 is a component of multiple recognition systems used by macrophages to phagocytose apoptotic lymphocytes. Cell death Differ. 1999;6:583–92.
pubmed: 10381656
doi: 10.1038/sj.cdd.4400529
dos-Santos D, Salina AC, Rodrigues TS, Rocha MF, Freitas-Filho EG, Alzamora-Terrel DL, et al. Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory programming and continual clearance of apoptotic cells. medRxiv. 2021.
Cheshenko N, Pierce C, Herold BC. Herpes simplex viruses activate phospholipid scramblase to redistribute phosphatidylserines and Akt to the outer leaflet of the plasma membrane and promote viral entry. PLoS Pathog. 2018;14:e1006766.
pubmed: 29293671
pmcid: 5766253
doi: 10.1371/journal.ppat.1006766
Wu N, Cernysiov V, Davidson D, Song H, Tang J, Luo S, et al. Critical role of lipid scramblase TMEM16F in phosphatidylserine exposure and repair of plasma membrane after pore formation. Cell Rep. 2020;30:1129–40. e5.
pubmed: 31995754
pmcid: 7104872
doi: 10.1016/j.celrep.2019.12.066
Kawano M, Nagata S. Efferocytosis and autoimmune disease. Int Immunol. 2018;30:551–8.
pubmed: 30165442
pmcid: 6234909
Erwig L, Henson P. Clearance of apoptotic cells by phagocytes. Cell Death Differ. 2008;15:243–50.
pubmed: 17571081
doi: 10.1038/sj.cdd.4402184
Yurdagul A Jr, Subramanian M, Wang X, Crown SB, Ilkayeva OR, Darville L, et al. Macrophage metabolism of apoptotic cell-derived arginine promotes continual efferocytosis and resolution of injury. Cell Metab. 2020;31:518–33. e10.
pubmed: 32004476
pmcid: 7173557
doi: 10.1016/j.cmet.2020.01.001
Zhang W, Zhao J, Wang R, Jiang M, Ye Q, Smith AD, et al. Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain. CNS Neurosci Ther. 2019;25:1329–42.
pubmed: 31697040
pmcid: 6887920
doi: 10.1111/cns.13256
Kourtzelis I, Hajishengallis G, Chavakis T. Phagocytosis of apoptotic cells in resolution of inflammation. Front Immunol. 2020;11:553
pubmed: 32296442
pmcid: 7137555
doi: 10.3389/fimmu.2020.00553
Chen W, Li L, Wang J, Zhang R, Zhang T, Wu Y, et al. The ABCA1-efferocytosis axis: a new strategy to protect against atherosclerosis. Clinica Chimica Acta. 2021;518:1–8.
doi: 10.1016/j.cca.2021.02.025
Myers KV, Amend SR, Pienta KJ. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment. Mol Cancer. 2019;18:019–1022.
doi: 10.1186/s12943-019-1022-2
Zhou Y, Fei M, Zhang G, Liang WC, Lin W, Wu Y, et al. Blockade of the phagocytic receptor MerTK on tumor-associated macrophages enhances P2X7R-dependent STING activation by tumor-derived cGAMP. Immunity 2020;52:357–73.
pubmed: 32049051
doi: 10.1016/j.immuni.2020.01.014
Chauhan AS, Kumar M, Chaudhary S, Patidar A, Dhiman A, Sheokand N, et al. Moonlighting glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells. FASEB J. 2017;31:2638–48.
pubmed: 28298336
doi: 10.1096/fj.201600982R
Sheokand N, Kumar S, Malhotra H, Tillu V, Raje CI, Raje M. Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition. Biochimica et Biophysica Acta. 2013;1830:3816–27.
pubmed: 23541988
doi: 10.1016/j.bbagen.2013.03.019
Swamydas M, Luo Y, Dorf ME, Lionakis MS. Isolation of mouse neutrophils. Curr Protoc Immunol. 2015;110:3.20.1–3.15.
doi: 10.1002/0471142735.im0320s110
Dalli J, Jones CP, Cavalcanti DM, Farsky SH, Perretti M, Rankin SM. Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow. FASEB J. 2012;26:387–96.
pubmed: 21957127
pmcid: 3250241
doi: 10.1096/fj.11-182089
Perskvist N, Long M, Stendahl O, Zheng L. Mycobacterium tuberculosis promotes apoptosis in human neutrophils by activating caspase-3 and altering expression of Bax/Bcl-xL via an oxygen-dependent pathway. J Immunol. 2002;168:6358–65.
pubmed: 12055253
doi: 10.4049/jimmunol.168.12.6358
Alemán M, Schierloh P, Silvia S, Musella RM, Saab MA, Baldini M, et al. Mycobacterium tuberculosis triggers apoptosis in peripheral neutrophils involving toll-like receptor 2 and p38 mitogen protein kinase in tuberculosis patients. Infect Immun. 2004;72:5150–8.
pubmed: 15322009
pmcid: 517458
doi: 10.1128/IAI.72.9.5150-5158.2004
Cocco RE, Ucker DS. Distinct modes of macrophage recognition for apoptotic and necrotic cells are not specified exclusively by phosphatidylserine exposure. Mol Biol Cell. 2001;12:919–30.
pubmed: 11294896
pmcid: 32276
doi: 10.1091/mbc.12.4.919
Wu Y, Singh S, Georgescu M-M, Birge RB. A role for Mer tyrosine kinase in αvβ5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci. 2005;118:539–53.
pubmed: 15673687
doi: 10.1242/jcs.01632
Fucikova J, Kralikova P, Fialova A, Brtnicky T, Rob L, Bartunkova J. et al. Human tumor cells killed by anthracyclines induce a tumor-specific immune response. Cancer Res. 2011;71:4821–33.
pubmed: 21602432
doi: 10.1158/0008-5472.CAN-11-0950
Rosenwald M, Koppe U, Keppeler H, Sauer G, Hennel R, Ernst A. et al. Serum-derived plasminogen is activated by apoptotic cells and promotes their phagocytic clearance. J Immunol. 2012;189:5722–8.
pubmed: 23150713
doi: 10.4049/jimmunol.1200922
Berghold VM, Gauster M, Hemmings DG, Moser G, Kremshofer J, Siwetz M, et al. Phospholipid scramblase 1 (PLSCR1) in villous trophoblast of the human placenta. Histochem Cell Biol. 2015;143:381–96.
pubmed: 25362260
doi: 10.1007/s00418-014-1294-y
Shevchenko A, Tomas H, Havli J, Olsen JV, Mann M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2006;1:2856–60.
pubmed: 17406544
doi: 10.1038/nprot.2006.468