Nature Communications (Dec 2018)
Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks
- Melanie Meister-Broekema,
- Rebecca Freilich,
- Chandhuru Jagadeesan,
- Jennifer N. Rauch,
- Rocio Bengoechea,
- William W. Motley,
- E. F. Elsiena Kuiper,
- Melania Minoia,
- Gabriel V. Furtado,
- Maria A. W. H. van Waarde,
- Shawn J. Bird,
- Adriana Rebelo,
- Stephan Zuchner,
- Peter Pytel,
- Steven S. Scherer,
- Federica F. Morelli,
- Serena Carra,
- Conrad C. Weihl,
- Steven Bergink,
- Jason E. Gestwicki,
- Harm H. Kampinga
Affiliations
- Melanie Meister-Broekema
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Rebecca Freilich
- Institute for Neurodegenerative Disease, University of California at San Francisco
- Chandhuru Jagadeesan
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Jennifer N. Rauch
- Institute for Neurodegenerative Disease, University of California at San Francisco
- Rocio Bengoechea
- Department of Neurology, Washington University School of Medicine
- William W. Motley
- Department of Neurology, Johns Hopkins School of Medicine
- E. F. Elsiena Kuiper
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Melania Minoia
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Gabriel V. Furtado
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Maria A. W. H. van Waarde
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Shawn J. Bird
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania
- Adriana Rebelo
- Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami
- Stephan Zuchner
- Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami
- Peter Pytel
- Department of Neuropathology, University of Chicago Pritzker School of Medicine
- Steven S. Scherer
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania
- Federica F. Morelli
- Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Nanotechnology, University of Modena and Reggio Emilia Modena
- Serena Carra
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Conrad C. Weihl
- Department of Neurology, Washington University School of Medicine
- Steven Bergink
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- Jason E. Gestwicki
- Institute for Neurodegenerative Disease, University of California at San Francisco
- Harm H. Kampinga
- University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cell & Systems
- DOI
- https://doi.org/10.1038/s41467-018-07718-5
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 14
Abstract
BAG3 is a Hsp70 co-chaperone that is highly expressed in muscles. Here the authors show that several myofibrillar myopathy causing BAG3 mutations are not impaired in Hsp70 binding, but rather impair the ADP-ATP exchange step of the Hsp70 cycle, causing the aggregation of BAG3, Hsp70 and Hsp70 clients and leading to a collapse of protein homeostasis.
