Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

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 AlbertiRossella Rota, Anat Ben-Zvi, Ritwick Sawarkar, Serena Carra

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article number452
JournalCell Death and Disease
Volume12
Issue number5
DOIs
StatePublished - 1 May 2021

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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