Cell Stress and Chaperones

, Volume 22, Issue 4, pp 531–540 | Cite as

An interaction study in mammalian cells demonstrates weak binding of HSPB2 to BAG3, which is regulated by HSPB3 and abrogated by HSPB8

  • Federica F. Morelli
  • Laura Mediani
  • Lonneke Heldens
  • Jessika Bertacchini
  • Ilaria Bigi
  • Arianna Dorotea Carrà
  • Jonathan Vinet
  • Serena Carra


The ten mammalian small heat shock proteins (sHSPs/HSPBs) show a different expression profile, although the majority of them are abundant in skeletal and cardiac muscles. HSPBs form hetero-oligomers and homo-oligomers by interacting together and complexes containing, e.g., HSPB2/HSPB3 or HSPB1/HSPB5 have been documented in mammalian cells and muscles. Moreover, HSPB8 associates with the Hsc70/Hsp70 co-chaperone BAG3, in mammalian, skeletal, and cardiac muscle cells. Interaction of HSPB8 with BAG3 regulates its stability and function. Weak association of HSPB5 and HSPB6 with BAG3 has been also reported upon overexpression in cells, supporting the idea that BAG3 might indirectly modulate the function of several HSPBs. However, it is yet unknown whether other HSPBs highly expressed in muscles such as HSPB2 and HSPB3 also bind to BAG3. Here, we report that in mammalian cells, upon overexpression, HSPB2 binds to BAG3 with an affinity weaker than HSPB8. HSPB2 competes with HSPB8 for binding to BAG3. In contrast, HSPB3 negatively regulates HSPB2 association with BAG3. In human myoblasts that express HSPB2, HSPB3, HSPB8, and BAG3, the latter interacts selectively with HSPB8. Combining these data, it supports the interpretation that HSPB8-BAG3 is the preferred interaction.


Small heat shock proteins/HSPBs BAG3 Interaction Competition 



We thank Prof. E. Pegoraro and Dr. E. Galletta for providing the LHCNM2 cells and for useful technical support for their use. SC is grateful to Prof. Harm H. Kampinga for useful discussions and tools. SC is grateful to Telethon (GEP12008 and GGP15001) and Association Francaise contres les Myopathies (grant number 15999) for financial support. SC also thanks the Centro Interdipartimentale Grandi Strumenti (CIGS) of the University of Modena and Reggio Emilia for support with confocal microscopy.


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Copyright information

© Cell Stress Society International 2017

Authors and Affiliations

  1. 1.Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Department of Cell BiologyUniversity Medical Center Groningen; University of GroningenGroningenThe Netherlands

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