Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03737-1 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Tatiana Tiago Barbara Hummel Federica F. Morelli Valentina Basile Jonathan Vinet Veronica Galli Laura Mediani Francesco Antoniani Silvia Pomella Matteo Cassandri Maria Giovanna Garone Beatrice Silvestri Marco Cimino Giovanna Cenacchi Roberta Costa Vincent Mouly Ina Poser Esti Yeger-Lotem Alessandro Rosa Simon Alberti Rossella Rota Anat Ben-Zvi Ritwick Sawarkar Serena Carra |
| spellingShingle |
Tatiana Tiago Barbara Hummel Federica F. Morelli Valentina Basile Jonathan Vinet Veronica Galli Laura Mediani Francesco Antoniani Silvia Pomella Matteo Cassandri Maria Giovanna Garone Beatrice Silvestri Marco Cimino Giovanna Cenacchi Roberta Costa Vincent Mouly Ina Poser Esti Yeger-Lotem Alessandro Rosa Simon Alberti Rossella Rota Anat Ben-Zvi Ritwick Sawarkar Serena Carra Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor Cell Death and Disease |
| author_facet |
Tatiana Tiago Barbara Hummel Federica F. Morelli Valentina Basile Jonathan Vinet Veronica Galli Laura Mediani Francesco Antoniani Silvia Pomella Matteo Cassandri Maria Giovanna Garone Beatrice Silvestri Marco Cimino Giovanna Cenacchi Roberta Costa Vincent Mouly Ina Poser Esti Yeger-Lotem Alessandro Rosa Simon Alberti Rossella Rota Anat Ben-Zvi Ritwick Sawarkar Serena Carra |
| author_sort |
Tatiana Tiago |
| title |
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor |
| title_short |
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor |
| title_full |
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor |
| title_fullStr |
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor |
| title_full_unstemmed |
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor |
| title_sort |
small heat-shock protein hspb3 promotes myogenesis by regulating the lamin b receptor |
| publisher |
Nature Publishing Group |
| series |
Cell Death and Disease |
| issn |
2041-4889 |
| publishDate |
2021-05-01 |
| description |
Abstract 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. |
| url |
https://doi.org/10.1038/s41419-021-03737-1 |
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doaj-0cc422533b6e43feaa940a5cd07be56b2021-05-09T11:04:54ZengNature Publishing GroupCell Death and Disease2041-48892021-05-0112511910.1038/s41419-021-03737-1Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptorTatiana Tiago0Barbara Hummel1Federica F. Morelli2Valentina Basile3Jonathan Vinet4Veronica Galli5Laura Mediani6Francesco Antoniani7Silvia Pomella8Matteo Cassandri9Maria Giovanna Garone10Beatrice Silvestri11Marco Cimino12Giovanna Cenacchi13Roberta Costa14Vincent Mouly15Ina Poser16Esti Yeger-Lotem17Alessandro Rosa18Simon Alberti19Rossella Rota20Anat Ben-Zvi21Ritwick Sawarkar22Serena Carra23Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaMax Planck Institute of Immunobiology and EpigeneticsCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaDepartment of Oncohematology, Bambino Gesù Children’s Hospital, IRCCSDepartment of Oncohematology, Bambino Gesù Children’s Hospital, IRCCSDepartment of Biology and Biotechnologies “Charles Darwin”, Sapienza University of RomeDepartment of Biology and Biotechnologies “Charles Darwin”, Sapienza University of RomeCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaDepartment of Biomedical and Neuromotor Sciences DIBINEM, University of Bologna, Bologna, Italy; Centre for Applied Biomedical Research - CRBA, University of Bologna, IRCCS St. Orsola HospitalDepartment of Biomedical and Neuromotor Sciences DIBINEM, University of Bologna, Bologna, Italy; Centre for Applied Biomedical Research - CRBA, University of Bologna, IRCCS St. Orsola HospitalCentre de Recherche en Myologie, Sorbonne Université, Inserm, Institut de MyologieMax Planck Institute of Molecular Cell Biology and GeneticsDepartment of Clinical Biochemistry and Pharmacology and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the NegevDepartment of Biology and Biotechnologies “Charles Darwin”, Sapienza University of RomeBiotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität DresdenDepartment of Oncohematology, Bambino Gesù Children’s Hospital, IRCCSDepartment of Life Sciences, Ben-Gurion University of the NegevMax Planck Institute of Immunobiology and EpigeneticsCentre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio EmiliaAbstract 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.https://doi.org/10.1038/s41419-021-03737-1 |