Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
06 05 2021
06 05 2021
Historique:
received:
11
03
2021
accepted:
19
04
2021
revised:
16
04
2021
entrez:
7
5
2021
pubmed:
8
5
2021
medline:
15
10
2021
Statut:
epublish
Résumé
One of the critical events that regulates muscle cell differentiation is the replacement of the lamin B receptor (LBR)-tether with the lamin A/C (LMNA)-tether to remodel transcription and induce differentiation-specific genes. Here, we report that localization and activity of the LBR-tether are crucially dependent on the muscle-specific chaperone HSPB3 and that depletion of HSPB3 prevents muscle cell differentiation. We further show that HSPB3 binds to LBR in the nucleoplasm and maintains it in a dynamic state, thus promoting the transcription of myogenic genes, including the genes to remodel the extracellular matrix. Remarkably, HSPB3 overexpression alone is sufficient to induce the differentiation of two human muscle cell lines, LHCNM2 cells, and rhabdomyosarcoma cells. We also show that mutant R116P-HSPB3 from a myopathy patient with chromatin alterations and muscle fiber disorganization, forms nuclear aggregates that immobilize LBR. We find that R116P-HSPB3 is unable to induce myoblast differentiation and instead activates the unfolded protein response. We propose that HSPB3 is a specialized chaperone engaged in muscle cell differentiation and that dysfunctional HSPB3 causes neuromuscular disease by deregulating LBR.
Identifiants
pubmed: 33958580
doi: 10.1038/s41419-021-03737-1
pii: 10.1038/s41419-021-03737-1
pmc: PMC8102500
doi:
Substances chimiques
HSPB3 protein, human
0
Heat-Shock Proteins
0
Heat-Shock Proteins, Small
0
Receptors, Cytoplasmic and Nuclear
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
452Subventions
Organisme : Medical Research Council
ID : MC_UU_00025/8
Pays : United Kingdom
Références
Braun, T. & Gautel, M. Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis. Nat. Rev. 12, 349–361 (2011).
doi: 10.1038/nrm3118
Ungricht, R. & Kutay, U. Mechanisms and functions of nuclear envelope remodelling. Nat. Rev. 18, 229–245 (2017).
doi: 10.1038/nrm.2016.153
Brosig, M., Ferralli, J., Gelman, L., Chiquet, M. & Chiquet-Ehrismann, R. Interfering with the connection between the nucleus and the cytoskeleton affects nuclear rotation, mechanotransduction and myogenesis. Int. J. Biochem. Cell Biol. 42, 1717–1728 (2010).
pubmed: 20621196
doi: 10.1016/j.biocel.2010.07.001
Thorsteinsdottir, S., Deries, M., Cachaco, A. S. & Bajanca, F. The extracellular matrix dimension of skeletal muscle development. Dev. Biol. 354, 191–207 (2011).
pubmed: 21420400
doi: 10.1016/j.ydbio.2011.03.015
Ye, Q. & Worman, H. J. Primary structure analysis and lamin B and DNA binding of human LBR, an integral protein of the nuclear envelope inner membrane. J. Biol. Chem. 269, 11306–11311 (1994).
pubmed: 8157662
doi: 10.1016/S0021-9258(19)78126-5
Solovei, I. et al. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152, 584–598 (2013).
pubmed: 23374351
doi: 10.1016/j.cell.2013.01.009
Sala, A. J., Bott, L. C. & Morimoto, R. I. Shaping proteostasis at the cellular, tissue, and organismal level. J. Cell Biol. 216, 1231–1241 (2017).
pubmed: 28400444
pmcid: 5412572
doi: 10.1083/jcb.201612111
Bar-Lavan, Y. et al. A differentiation transcription factor establishes muscle-specific proteostasis in Caenorhabditis elegans. PLoS Genet. 12, e1006531 (2016).
pubmed: 28036392
pmcid: 5201269
doi: 10.1371/journal.pgen.1006531
Echeverria, P. C., Briand, P. A. & Picard, D. A remodeled Hsp90 molecular chaperone ensemble with the novel cochaperone Aarsd1 is required for muscle differentiation. Mol. Cell Biol. 36, 1310–1321 (2016).
pubmed: 26884463
pmcid: 4836269
doi: 10.1128/MCB.01099-15
Ghosh, A. & Som, A. RNA-Seq analysis reveals pluripotency-associated genes and their interaction networks in human embryonic stem cells. Comput. Biol. Chem. 85, 107239 (2020).
pubmed: 32109853
doi: 10.1016/j.compbiolchem.2020.107239
Sugiyama, Y. et al. Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation. J. Biol. Chem. 275, 1095–1104 (2000).
pubmed: 10625651
doi: 10.1074/jbc.275.2.1095
Molyneaux, B. J. et al. Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons. J. Neurosci. 29, 12343–12354 (2009).
pubmed: 19793993
pmcid: 2776075
doi: 10.1523/JNEUROSCI.6108-08.2009
Boelens, W. C., Van Boekel, M. A. & De Jong, W. W. HspB3, the most deviating of the six known human small heat shock proteins. Biochimica et. biophysica acta 1388, 513–516 (1998).
pubmed: 9858786
doi: 10.1016/S0167-4838(98)00215-5
La Padula, V. et al. HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration. Exp. Neurol. 286, 40–49 (2016).
pubmed: 27567740
doi: 10.1016/j.expneurol.2016.08.014
Kappe, G. et al. The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones. 8, 53–61 (2003).
pubmed: 12820654
pmcid: 514853
doi: 10.1379/1466-1268(2003)8<53:THGECS>2.0.CO;2
Haslbeck, M., Weinkauf, S. & Buchner, J. Small heat shock proteins: simplicity meets complexity. J. Biol. Chem. 294, 2121–2132 (2019).
pubmed: 30385502
doi: 10.1074/jbc.REV118.002809
de Thonel, A., Le Mouel, A. & Mezger, V. Transcriptional regulation of small HSP-HSF1 and beyond. Int. J. Biochem. Cell Biol. 44, 1593–1612 (2012).
pubmed: 22750029
doi: 10.1016/j.biocel.2012.06.012
Morelli, F. F. et al. Aberrant compartment formation by HSPB2 mislocalizes lamin A and compromises nuclear integrity and function. Cell Rep. 20, 2100–2115 (2017).
pubmed: 28854361
pmcid: 5583511
doi: 10.1016/j.celrep.2017.08.018
Shemesh, N. et al. The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones. Nat. Commun. 12, 1–16 (2021).
doi: 10.1038/s41467-021-22369-9
Skapek, S. X. et al. Rhabdomyosarcoma. Nat. Rev. Dis. Prim. 5, 1 (2019).
pubmed: 30617281
doi: 10.1038/s41572-018-0051-2
Zhu, C. H. et al. Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies. Aging Cell. 6, 515–523 (2007).
pubmed: 17559502
doi: 10.1111/j.1474-9726.2007.00306.x
den Engelsman, J. et al. The small heat-shock proteins HSPB2 and HSPB3 form well-defined heterooligomers in a unique 3 to 1 subunit ratio. J. Mol. Biol. 393, 1022–1032 (2009).
doi: 10.1016/j.jmb.2009.08.052
Lenzi, J. et al. Differentiation of control and ALS mutant human iPSCs into functional skeletal muscle cells, a tool for the study of neuromuscolar diseases. Stem Cell Res. 17, 140–147 (2016).
pubmed: 27318155
pmcid: 5009183
doi: 10.1016/j.scr.2016.06.003
Jost, K. L. et al. Gene repositioning within the cell nucleus is not random and is determined by its genomic neighborhood. Epigenet. Chromatin 8, 36 (2015).
doi: 10.1186/s13072-015-0025-5
Brero, A. et al. Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J. Cell Biol. 169, 733–743 (2005).
pubmed: 15939760
pmcid: 2171616
doi: 10.1083/jcb.200502062
Ye, Q. & Worman, H. J. Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. J. Biol. Chem. 271, 14653–14656 (1996).
pubmed: 8663349
doi: 10.1074/jbc.271.25.14653
Ye, Q., Callebaut, I., Pezhman, A., Courvalin, J. C. & Worman, H. J. Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J. Biol. Chem. 272, 14983–14989 (1997).
pubmed: 9169472
doi: 10.1074/jbc.272.23.14983
Soullam, B. & Worman, H. J. The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal. J. Cell Biol. 120, 1093–1100 (1993).
pubmed: 7679672
doi: 10.1083/jcb.120.5.1093
Smith, S. & Blobel, G. The first membrane spanning region of the lamin B receptor is sufficient for sorting to the inner nuclear membrane. J. Cell Biol. 120, 631–637 (1993).
pubmed: 8381121
doi: 10.1083/jcb.120.3.631
Mudumbi, K. C. et al. Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores. Nat. Commun. 11, 2184 (2020).
pubmed: 32366843
pmcid: 7198523
doi: 10.1038/s41467-020-16033-x
Liu, B., Jin, D. Y. & Zhou, Z. From loss to gain: role for SUN1 in laminopathies. Cell Biosci. 2, 21 (2012).
pubmed: 22709970
pmcid: 3419603
doi: 10.1186/2045-3701-2-21
Tsai, P. L., Zhao, C., Turner, E. & Schlieker, C. The lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. eLife 5, e16011 (2016).
pubmed: 27336722
pmcid: 4951196
doi: 10.7554/eLife.16011
Mendez-Lopez, I. & Worman, H. J. Inner nuclear membrane proteins: impact on human disease. Chromosoma 121, 153–167 (2012).
pubmed: 22307332
doi: 10.1007/s00412-012-0360-2
Giannios, I., Chatzantonaki, E. & Georgatos, S. Dynamics and structure-function relationships of the lamin B receptor (LBR). PLoS ONE 12, e0169626 (2017).
pubmed: 28118363
pmcid: 5261809
doi: 10.1371/journal.pone.0169626
Ellenberg, J. et al. Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis. J. Cell Biol. 138, 1193–1206 (1997).
pubmed: 9298976
pmcid: 2132565
doi: 10.1083/jcb.138.6.1193
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. 18, 285–298 (2017).
doi: 10.1038/nrm.2017.7
Sudnitsyna, M. V., Mymrikov, E. V., Seit-Nebi, A. S. & Gusev, N. B. The role of intrinsically disordered regions in the structure and functioning of small heat shock proteins. Curr. Protein Pept. Sci. 13, 76–85 (2012).
pubmed: 22044147
doi: 10.2174/138920312799277875
Nikolakaki, E., Mylonis, I. & Giannakouros, T. Lamin B receptor: interplay between structure, function and localization. Cells. 6, 28 (2017).
pmcid: 5617974
doi: 10.3390/cells6030028
Poser, I. et al. BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals. Nat. Methods 5, 409–415 (2008).
pubmed: 18391959
pmcid: 2871289
doi: 10.1038/nmeth.1199
Naba, A. et al. The extracellular matrix: tools and insights for the “omics” era. Matrix Biol. 49, 10–24 (2016).
pubmed: 26163349
doi: 10.1016/j.matbio.2015.06.003
Csapo, R., Gumpenberger, M. & Wessner, B. Skeletal muscle extracellular matrix—what do we know about its composition, regulation, and physiological roles? A narrative review. Front. Physiol. 11, 253 (2020).
pubmed: 32265741
pmcid: 7096581
doi: 10.3389/fphys.2020.00253
Goody, M. F., Sher, R. B. & Henry, C. A. Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease. Dev. Biol. 401, 75–91 (2015).
pubmed: 25592225
pmcid: 4402131
doi: 10.1016/j.ydbio.2015.01.002
Hynes, R. O. & Naba, A. Overview of the matrisome-an inventory of extracellular matrix constituents and functions. Cold Spring Harb. Perspect. Biol. 4, a004903 (2012).
pubmed: 21937732
pmcid: 3249625
doi: 10.1101/cshperspect.a004903
Li, Y. et al. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol. Ther. 15, 1616–1622 (2007).
pubmed: 17609657
doi: 10.1038/sj.mt.6300250
Oh, S. W. et al. Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton. J. Cell Sci. 116, 2261–2275 (2003).
pubmed: 12711699
doi: 10.1242/jcs.00422
Gagan, J., Dey, B. K., Layer, R., Yan, Z. & Dutta, A. Notch3 and Mef2c proteins are mutually antagonistic via Mkp1 protein and miR-1/206 microRNAs in differentiating myoblasts. J. Biol. Chem. 287, 40360–40370 (2012).
pubmed: 23055528
pmcid: 3504751
doi: 10.1074/jbc.M112.378414
Berkes, C. A. & Tapscott, S. J. MyoD and the transcriptional control of myogenesis. Semin Cell Dev. Biol. 16, 585–595 (2005).
pubmed: 16099183
doi: 10.1016/j.semcdb.2005.07.006
Williamson, D. et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J. Clin. Oncol. 28, 2151–2158 (2010).
pubmed: 20351326
doi: 10.1200/JCO.2009.26.3814
Gartrell, J. & Pappo, A. Recent advances in understanding and managing pediatric rhabdomyosarcoma. F1000 Faculty Rev-685. 9, (2020). https://doi.org/10.12688/f1000research.22451.1 .
Gryder, B. E. et al. Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma. Nat. Genet. 51, 1714–1722 (2019).
pubmed: 31784732
pmcid: 6886578
doi: 10.1038/s41588-019-0534-4
Tenente, I. M. et al. Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. eLife 6, e19214 (2017).
pubmed: 28080960
pmcid: 5231408
doi: 10.7554/eLife.19214
Kolb, S. J. et al. Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. Neurology 74, 502–506 (2010).
pubmed: 20142617
doi: 10.1212/WNL.0b013e3181cef84a
Nam, D. E. et al. Small heat shock protein B3 (HSPB3) mutation in an axonal Charcot-Marie-Tooth disease family. J. Peripher Nerv. Syst. 23, 60–66 (2018).
pubmed: 29341343
doi: 10.1111/jns.12249
Kouroku, Y. et al. Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation. Hum. Mol. Genet. 11, 1505–1515 (2002).
pubmed: 12045204
doi: 10.1093/hmg/11.13.1505
Hetz, C. & Saxena, S. ER stress and the unfolded protein response in neurodegeneration. Nat. Rev. Neurol. 13, 477–491 (2017).
pubmed: 28731040
doi: 10.1038/nrneurol.2017.99
Deldicque, L. et al. The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the downregulation of protein synthesis. Am. J. Physiol. Endocrinol. Metab. 299, E695–E705 (2010).
pubmed: 20501874
doi: 10.1152/ajpendo.00038.2010
Wu, J. et al. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1alpha/ATF6alpha complex. Cell Metab. 13, 160–169 (2011).
pubmed: 21284983
pmcid: 3057411
doi: 10.1016/j.cmet.2011.01.003
Ikezoe, K. et al. Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. Acta Neuropathol. 114, 527–535 (2007).
pubmed: 17661063
doi: 10.1007/s00401-007-0267-9
Nogalska, A., Wojcik, S., Engel, W. K., McFerrin, J. & Askanas, V. Endoplasmic reticulum stress induces myostatin precursor protein and NF-kappaB in cultured human muscle fibers: relevance to inclusion body myositis. Exp. Neurol. 204, 610–618 (2007).
pubmed: 17261282
doi: 10.1016/j.expneurol.2006.12.014
Zito, E. Targeting ER stress/ER stress response in myopathies. Redox Biol. 26, 101232 (2019).
pubmed: 31181458
pmcid: 6556854
doi: 10.1016/j.redox.2019.101232
Koch, B. & Yu, H. G. Regulation of inner nuclear membrane associated protein degradation. Nucleus 10, 169–180 (2019).
pubmed: 31313624
pmcid: 6682350
doi: 10.1080/19491034.2019.1644593
Makatsori, D. et al. The inner nuclear membrane protein lamin B receptor forms distinct microdomains and links epigenetically marked chromatin to the nuclear envelope. J. Biol. Chem. 279, 25567–25573 (2004).
pubmed: 15056654
doi: 10.1074/jbc.M313606200
Nikolakaki, E. et al. RNA association or phosphorylation of the RS domain prevents aggregation of RS domain-containing proteins. Biochimica et. biophysica acta 1780, 214–225 (2008).
pubmed: 18022399
doi: 10.1016/j.bbagen.2007.10.014
Haynes, C. & Iakoucheva, L. M. Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins. Nucleic Acids Res. 34, 305–312 (2006).
pubmed: 16407336
pmcid: 1326245
doi: 10.1093/nar/gkj424
Worman, H. J., Ostlund, C. & Wang, Y. Diseases of the nuclear envelope. Cold Spring Harb. Perspect. Biol. 2, a000760 (2010).
pubmed: 20182615
pmcid: 2828284
doi: 10.1101/cshperspect.a000760
Lytridou, A. A. et al. Stbd1 promotes glycogen clustering during endoplasmic reticulum stress and supports survival of mouse myoblasts. J. Cell Sci. 133, jcs244855. (2020). https://doi.org/10.1242/jcs.244855 .
Le Grand, F. & Rudnicki, M. A. Skeletal muscle satellite cells and adult myogenesis. Curr. Opin. Cell Biol. 19, 628–633 (2007).
pubmed: 17996437
pmcid: 2215059
doi: 10.1016/j.ceb.2007.09.012
Charge, S. B. & Rudnicki, M. A. Cellular and molecular regulation of muscle regeneration. Physiol. Rev. 84, 209–238 (2004).
pubmed: 14715915
doi: 10.1152/physrev.00019.2003
de Luca, A. C., Lacour, S. P., Raffoul, W. & di Summa, P. G. Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen. Res. 9, 1943–1948 (2014).
pubmed: 25598773
pmcid: 4283273
doi: 10.4103/1673-5374.145366
Carosio, S., Berardinelli, M. G., Aucello, M. & Musaro, A. Impact of ageing on muscle cell regeneration. Ageing Res. Rev. 10, 35–42 (2011).
pubmed: 19683075
doi: 10.1016/j.arr.2009.08.001
Cohen, T. V., Cohen, J. E. & Partridge, T. A. Myogenesis in dysferlin-deficient myoblasts is inhibited by an intrinsic inflammatory response. Neuromuscul. Disord. 22, 648–658 (2012).
pubmed: 22560623
pmcid: 4147957
doi: 10.1016/j.nmd.2012.03.002
Boyden, S. E. et al. Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores. Neurogenetics 13, 115–124 (2012).
pubmed: 22371254
pmcid: 3332380
doi: 10.1007/s10048-012-0315-z
Shi, C. H. et al. Recessive hereditary motor and sensory neuropathy caused by IGHMBP2 gene mutation. Neurology 85, 383–384 (2015).
pubmed: 26136520
pmcid: 4520818
doi: 10.1212/WNL.0000000000001747
Liu, J. et al. MORC2 regulates C/EBPalpha-mediated cell differentiation via sumoylation. Cell Death Differ. 26, 1905–1917 (2019).
pubmed: 30644437
pmcid: 6748086
doi: 10.1038/s41418-018-0259-4
Echaniz-Laguna, A. et al. NDRG1-linked Charcot-Marie-Tooth disease (CMT4D) with central nervous system involvement. Neuromuscul. Disord. 17, 163–168 (2007).
pubmed: 17142040
doi: 10.1016/j.nmd.2006.10.002
Nakhro, K. et al. SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3. Neurology 81, 165–173 (2013).
pubmed: 23749797
doi: 10.1212/WNL.0b013e31829a3421
Lassuthova, P. et al. Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2. Clin. Genet. 94, 467–472 (2018).
pubmed: 30028002
doi: 10.1111/cge.13417
Lenzi, J. et al. ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cell-derived motoneurons. Dis. Model Mech. 8, 755–766 (2015).
pubmed: 26035390
pmcid: 4486861
Poulet, A. et al. NucleusJ: an ImageJ plugin for quantifying 3D images of interphase nuclei. Bioinformatics 31, 1144–1146 (2015).
pubmed: 25416749
doi: 10.1093/bioinformatics/btu774
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysisof systems-level datasets. Nature communications 10, 1523 (2019).
pubmed: 30944313
pmcid: 6447622
doi: 10.1038/s41467-019-09234-6