The IRE1α/XBP1 signaling axis drives myoblast fusion in adult skeletal muscle.
IRE1
Muscle Regeneration
Myoblast Fusion
XBP1
and Myomaker
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
received:
22
11
2023
accepted:
17
06
2024
revised:
29
05
2024
medline:
10
7
2024
pubmed:
10
7
2024
entrez:
9
7
2024
Statut:
aheadofprint
Résumé
Skeletal muscle regeneration involves a signaling network that regulates the proliferation, differentiation, and fusion of muscle precursor cells to injured myofibers. IRE1α, one of the arms of the unfolded protein response, regulates cellular proteostasis in response to ER stress. Here, we demonstrate that inducible deletion of IRE1α in satellite cells of mice impairs skeletal muscle regeneration through inhibiting myoblast fusion. Knockdown of IRE1α or its downstream target, X-box protein 1 (XBP1), also inhibits myoblast fusion during myogenesis. Transcriptome analysis revealed that knockdown of IRE1α or XBP1 dysregulates the gene expression of molecules involved in myoblast fusion. The IRE1α-XBP1 axis mediates the gene expression of multiple profusion molecules, including myomaker (Mymk). Spliced XBP1 (sXBP1) transcription factor binds to the promoter of Mymk gene during myogenesis. Overexpression of myomaker in IRE1α-knockdown cultures rescues fusion defects. Inducible deletion of IRE1α in satellite cells also inhibits myoblast fusion and myofiber hypertrophy in response to functional overload. Collectively, our study demonstrates that IRE1α promotes myoblast fusion through sXBP1-mediated up-regulation of the gene expression of multiple profusion molecules, including myomaker.
Identifiants
pubmed: 38982191
doi: 10.1038/s44319-024-00197-4
pii: 10.1038/s44319-024-00197-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR081487
Organisme : HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ID : AR059810
Informations de copyright
© 2024. The Author(s).
Références
Abmayr SM, Pavlath GK (2012) Myoblast fusion: lessons from flies and mice. Development 139:641–656
pubmed: 22274696
pmcid: 3265056
doi: 10.1242/dev.068353
Acosta-Alvear D, Karagoz GE, Frohlich F, Li H, Walther TC, Walter P (2018) The unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1. Elife 7:e43036
pubmed: 30582518
pmcid: 6336407
doi: 10.7554/eLife.43036
Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht BD (2007) XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell 27:53–66
pubmed: 17612490
doi: 10.1016/j.molcel.2007.06.011
Adams CJ, Kopp MC, Larburu N, Nowak PR, Ali MMU (2019) Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci 6:11
pubmed: 30931312
pmcid: 6423427
doi: 10.3389/fmolb.2019.00011
Afroze D, Kumar A (2019) ER stress in skeletal muscle remodeling and myopathies. FEBS J 286:379–398
pubmed: 29239106
doi: 10.1111/febs.14358
Beauchamp JR, Heslop L, Yu DS, Tajbakhsh S, Kelly RG, Wernig A, Buckingham ME, Partridge TA, Zammit PS (2000) Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol 151:1221–1234
pubmed: 11121437
pmcid: 2190588
doi: 10.1083/jcb.151.6.1221
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B Methodol 57:289–300
doi: 10.1111/j.2517-6161.1995.tb02031.x
Bi P, Ramirez-Martinez A, Li H, Cannavino J, McAnally JR, Shelton JM, Sanchez-Ortiz E, Bassel-Duby R, Olson EN (2017) Control of muscle formation by the fusogenic micropeptide myomixer. Science 356:323–327
pubmed: 28386024
pmcid: 5502127
doi: 10.1126/science.aam9361
Bohnert KR, McMillan JD, Kumar A (2018) Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease. J Cell Physiol 233:67–78
pubmed: 28177127
doi: 10.1002/jcp.25852
Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA (2008) A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell 2:50–59
pubmed: 18371421
doi: 10.1016/j.stem.2007.10.006
Buckingham M, Bajard L, Chang T, Daubas P, Hadchouel J, Meilhac S, Montarras D, Rocancourt D, Relaix F (2003) The formation of skeletal muscle: from somite to limb. J Anat 202:59–68
pubmed: 12587921
pmcid: 1571050
doi: 10.1046/j.1469-7580.2003.00139.x
Cheneby J, Gheorghe M, Artufel M, Mathelier A, Ballester B (2018) ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments. Nucleic Acids Res 46:D267–D275
pubmed: 29126285
doi: 10.1093/nar/gkx1092
Cheneby J, Menetrier Z, Mestdagh M, Rosnet T, Douida A, Rhalloussi W, Bergon A, Lopez F, Ballester B (2020) ReMap 2020: a database of regulatory regions from an integrative analysis of Human and Arabidopsis DNA-binding sequencing experiments. Nucleic Acids Res 48:D180–D188
pubmed: 31665499
Gardner BM, Walter P (2011) Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 333:1891–1894
pubmed: 21852455
pmcid: 3202989
doi: 10.1126/science.1209126
Goh Q, Millay DP (2017) Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy. Elife 6:e20007
pubmed: 28186492
pmcid: 5338923
doi: 10.7554/eLife.20007
Grandjean JMD, Madhavan A, Cech L, Seguinot BO, Paxman RJ, Smith E, Scampavia L, Powers ET, Cooley CB, Plate L et al (2020) Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming. Nat Chem Biol 16:1052–1061
pubmed: 32690944
pmcid: 7502540
doi: 10.1038/s41589-020-0584-z
Griffon A, Barbier Q, Dalino J, van Helden J, Spicuglia S, Ballester B (2015) Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape. Nucleic Acids Res 43:e27
pubmed: 25477382
doi: 10.1093/nar/gku1280
Gu Z, Hubschmann D (2022) Make interactive complex heatmaps in R. Bioinformatics 38:1460–1462
pubmed: 34864868
doi: 10.1093/bioinformatics/btab806
Hammal F, de Langen P, Bergon A, Lopez F, Ballester B (2022) ReMap 2022: a database of human, mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments. Nucleic Acids Res 50:D316–D325
pubmed: 34751401
doi: 10.1093/nar/gkab996
Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195–2224
pubmed: 15371334
doi: 10.1101/gad.1228704
He S, Fu T, Yu Y, Liang Q, Li L, Liu J, Zhang X, Zhou Q, Guo Q, Xu D et al (2021) IRE1alpha regulates skeletal muscle regeneration through myostatin mRNA decay. J Clin Invest 131:e143737
pubmed: 34283807
pmcid: 8409588
doi: 10.1172/JCI143737
Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol cell Biol 13:89–102
pubmed: 22251901
doi: 10.1038/nrm3270
Hetz C, Axten JM, Patterson JB (2019) Pharmacological targeting of the unfolded protein response for disease intervention. Nat Chem Biol 15:764–775
pubmed: 31320759
doi: 10.1038/s41589-019-0326-2
Hetz C, Chevet E, Oakes SA (2015) Proteostasis control by the unfolded protein response. Nat Cell Biol 17:829–838
pubmed: 26123108
pmcid: 5546321
doi: 10.1038/ncb3184
Hetz C, Zhang K, Kaufman RJ (2020) Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol cell Biol 21:421–438
pubmed: 32457508
pmcid: 8867924
doi: 10.1038/s41580-020-0250-z
Hindi SM, Kumar A (2016) TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis. J Clin Invest 126:151–168
pubmed: 26619121
doi: 10.1172/JCI81655
Hindi SM, Millay DP (2022) All for one and one for all: regenerating skeletal muscle. Cold Spring Harb Perspect Biol 14:a040824
pubmed: 34750174
doi: 10.1101/cshperspect.a040824
Hindi SM, Sato S, Xiong G, Bohnert KR, Gibb AA, Gallot YS, McMillan JD, Hill BG, Uchida S, Kumar A (2018) TAK1 regulates skeletal muscle mass and mitochondrial function. JCI Insight 3:e98441
pubmed: 29415881
pmcid: 5821216
doi: 10.1172/jci.insight.98441
Hindi SM, Shin J, Gallot YS, Straughn AR, Simionescu-Bankston A, Hindi L, Xiong G, Friedland RP, Kumar A (2017) MyD88 promotes myoblast fusion in a cell-autonomous manner. Nat Commun 8:1624
pubmed: 29158520
pmcid: 5696367
doi: 10.1038/s41467-017-01866-w
Hindi SM, Tajrishi MM, Kumar A (2013) Signaling mechanisms in mammalian myoblast fusion. Sci Signal 6:re2
pubmed: 23612709
pmcid: 3724417
doi: 10.1126/scisignal.2003832
Hochreiter-Hufford AE, Lee CS, Kinchen JM, Sokolowski JD, Arandjelovic S, Call JA, Klibanov AL, Yan Z, Mandell JW, Ravichandran KS (2013) Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497:263–267
pubmed: 23615608
pmcid: 3773542
doi: 10.1038/nature12135
Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS (2009) Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 186:323–331
pubmed: 19651891
pmcid: 2728407
doi: 10.1083/jcb.200903014
Iwawaki T, Akai R, Yamanaka S, Kohno K (2009) Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci USA 106:16657–16662
pubmed: 19805353
pmcid: 2757843
doi: 10.1073/pnas.0903775106
Kim JH, Jin P, Duan R, Chen EH (2015) Mechanisms of myoblast fusion during muscle development. Curr Opin Genet Dev 32:162–170
pubmed: 25989064
pmcid: 4508005
doi: 10.1016/j.gde.2015.03.006
Krauss RS (2010) Regulation of promyogenic signal transduction by cell-cell contact and adhesion. Exp cell Res 316:3042–3049
pubmed: 20471976
pmcid: 2945434
doi: 10.1016/j.yexcr.2010.05.008
Kuang S, Kuroda K, Le Grand F, Rudnicki MA (2007) Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell 129:999–1010
pubmed: 17540178
pmcid: 2718740
doi: 10.1016/j.cell.2007.03.044
Lin J, Liu H, Fukumoto T, Zundell J, Yan Q, Tang CA, Wu S, Zhou W, Guo D, Karakashev S et al (2021) Targeting the IRE1alpha/XBP1s pathway suppresses CARM1-expressing ovarian cancer. Nat Commun 12:5321
pubmed: 34493732
pmcid: 8423755
doi: 10.1038/s41467-021-25684-3
Liu L, Cai J, Wang H, Liang X, Zhou Q, Ding C, Zhu Y, Fu T, Guo Q, Xu Z et al (2019) Coupling of COPII vesicle trafficking to nutrient availability by the IRE1alpha-XBP1s axis. Proc Natl Acad Sci USA 116:11776–11785
pubmed: 31123148
pmcid: 6575159
doi: 10.1073/pnas.1814480116
Maurel M, Chevet E, Tavernier J, Gerlo S (2014) Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci 39:245–254
pubmed: 24657016
doi: 10.1016/j.tibs.2014.02.008
Millay DP, O’Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R, Olson EN (2013) Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature 499:301–305
pubmed: 23868259
pmcid: 3739301
doi: 10.1038/nature12343
Millay DP, Sutherland LB, Bassel-Duby R, Olson EN (2014) Myomaker is essential for muscle regeneration. Genes Dev 28:1641–1646
pubmed: 25085416
pmcid: 4117939
doi: 10.1101/gad.247205.114
Miyake M, Nomura A, Ogura A, Takehana K, Kitahara Y, Takahara K, Tsugawa K, Miyamoto C, Miura N, Sato R et al (2016) Skeletal muscle-specific eukaryotic translation initiation factor 2alpha phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism. FASEB J 30:798–812
pubmed: 26487695
doi: 10.1096/fj.15-275990
Nakanishi K, Dohmae N, Morishima N (2007) Endoplasmic reticulum stress increases myofiber formation in vitro. FASEB J 21:2994–3003
pubmed: 17435177
doi: 10.1096/fj.06-6408com
Park SM, Kang TI, So JS (2021) Roles of XBP1s in transcriptional regulation of target genes. Biomedicines 9:791
pubmed: 34356855
pmcid: 8301375
doi: 10.3390/biomedicines9070791
Quwaider D, Corchete LA, Martín-Izquierdo M, Hernández-Sánchez JM, Rojas EA, Cardona-Benavides IJ, García-Sanz R, Herrero AB, Gutiérrez NC (2022) RNA sequencing identifies novel regulated IRE1-dependent decay targets that affect multiple myeloma survival and proliferation. Exp Hematol Oncol 11:1–15
doi: 10.1186/s40164-022-00271-4
Razani B, Reichardt AD, Cheng G (2011) Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives. Immunol Rev 244:44–54
pubmed: 22017430
doi: 10.1111/j.1600-065X.2011.01059.x
Relaix F, Bencze M, Borok MJ, Der Vartanian A, Gattazzo F, Mademtzoglou D, Perez-Diaz S, Prola A, Reyes-Fernandez PC, Rotini A et al (2021) Perspectives on skeletal muscle stem cells. Nat Commun 12:692
pubmed: 33514709
pmcid: 7846784
doi: 10.1038/s41467-020-20760-6
Rochlin K, Yu S, Roy S, Baylies MK (2010) Myoblast fusion: when it takes more to make one. Dev Biol 341:66–83
pubmed: 19932206
doi: 10.1016/j.ydbio.2009.10.024
Roy A, Tomaz da Silva M, Bhat R, Bohnert KR, Iwawaki T, Kumar A (2021) The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism. Elife 10:e73215
pubmed: 34812145
pmcid: 8635982
doi: 10.7554/eLife.73215
Sampath SC, Sampath SC, Millay DP (2018) Myoblast fusion confusion: the resolution begins. Skelet Muscle 8:3
pubmed: 29386054
pmcid: 5793351
doi: 10.1186/s13395-017-0149-3
Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786
pubmed: 11030621
doi: 10.1016/S0092-8674(00)00066-0
Tan YY, Zhang Y, Li B, Ou YW, Xie SJ, Chen PP, Mei SQ, Huang QJ, Zheng LL, Qu LH (2021) PERK signaling controls myoblast differentiation by regulating microRNA networks. Front Cell Dev Biol 9:670435
pubmed: 34124052
pmcid: 8193987
doi: 10.3389/fcell.2021.670435
Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287:664–666
pubmed: 10650002
doi: 10.1126/science.287.5453.664
Wang M, Kaufman RJ (2014) The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 14:581–597
pubmed: 25145482
doi: 10.1038/nrc3800
Wu J, Kaufman RJ (2006) From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ 13:374–384
pubmed: 16397578
doi: 10.1038/sj.cdd.4401840
Wu R, Zhang QH, Lu YJ, Ren K, Yi GH (2015) Involvement of the IRE1alpha-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases. DNA Cell Biol 34:6–18
pubmed: 25216212
pmcid: 4281841
doi: 10.1089/dna.2014.2552
Xiong G, Hindi SM, Mann AK, Gallot YS, Bohnert KR, Cavener DR, Whittemore SR, Kumar A (2017) The PERK arm of the unfolded protein response regulates satellite cell-mediated skeletal muscle regeneration. Elife 6:e22871
pubmed: 28332979
pmcid: 5391206
doi: 10.7554/eLife.22871
Yin H, Price F, Rudnicki MA (2013) Satellite cells and the muscle stem cell niche. Physiol Rev 93:23–67
pubmed: 23303905
pmcid: 4073943
doi: 10.1152/physrev.00043.2011
Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891
pubmed: 11779464
doi: 10.1016/S0092-8674(01)00611-0
Zhang H, Wen J, Bigot A, Chen J, Shang R, Mouly V, Bi P (2020) Human myotube formation is determined by MyoD-Myomixer/Myomaker axis. Sci Adv 6:eabc4062
pubmed: 33355126
pmcid: 11206528
doi: 10.1126/sciadv.abc4062
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523
pubmed: 30944313
pmcid: 6447622
doi: 10.1038/s41467-019-09234-6
Zismanov V, Chichkov V, Colangelo V, Jamet S, Wang S, Syme A, Koromilas AE, Crist C (2016) Phosphorylation of eIF2alpha is a translational control mechanism regulating muscle stem cell quiescence and self-renewal. Cell Stem Cell 18:79–90
pubmed: 26549106
doi: 10.1016/j.stem.2015.09.020