BAG5 Promotes Alpha-Synuclein Oligomer Formation and Functionally Interacts With the Autophagy Adaptor Protein p62

Erik L. Friesen; Erik L. Friesen; Yu Tong Zhang; Yu Tong Zhang; Rebecca Earnshaw; Rebecca Earnshaw; Mitch L. De Snoo; Mitch L. De Snoo; Darren M. O’Hara; Darren M. O’Hara; Victoria Agapova; Hien Chau; Sophie Ngana; Sophie Ngana; Kevin S. Chen; Kevin S. Chen; Lorraine V. Kalia; Lorraine V. Kalia; Lorraine V. Kalia; Suneil K. Kalia; Suneil K. Kalia; Suneil K. Kalia

doi:10.3389/fcell.2020.00716

Frontiers in Cell and Developmental Biology (Aug 2020)

BAG5 Promotes Alpha-Synuclein Oligomer Formation and Functionally Interacts With the Autophagy Adaptor Protein p62

Erik L. Friesen,
Erik L. Friesen,
Yu Tong Zhang,
Yu Tong Zhang,
Rebecca Earnshaw,
Rebecca Earnshaw,
Mitch L. De Snoo,
Mitch L. De Snoo,
Darren M. O’Hara,
Darren M. O’Hara,
Victoria Agapova,
Hien Chau,
Sophie Ngana,
Sophie Ngana,
Kevin S. Chen,
Kevin S. Chen,
Lorraine V. Kalia,
Lorraine V. Kalia,
Lorraine V. Kalia,
Suneil K. Kalia,
Suneil K. Kalia,
Suneil K. Kalia

Affiliations

Erik L. Friesen: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Erik L. Friesen: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Yu Tong Zhang: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Yu Tong Zhang: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Rebecca Earnshaw: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Rebecca Earnshaw: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Mitch L. De Snoo: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Mitch L. De Snoo: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Darren M. O’Hara: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Darren M. O’Hara: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Victoria Agapova: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Hien Chau: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Sophie Ngana: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Sophie Ngana: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Kevin S. Chen: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Kevin S. Chen: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Lorraine V. Kalia: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Lorraine V. Kalia: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Lorraine V. Kalia: Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
Suneil K. Kalia: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Suneil K. Kalia: Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada
Suneil K. Kalia: Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

DOI: https://doi.org/10.3389/fcell.2020.00716
Journal volume & issue: Vol. 8

Abstract

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Molecular chaperones are critical to maintaining intracellular proteostasis and have been shown to have a protective role against alpha-synuclein-mediated toxicity. Co-chaperone proteins regulate the activity of molecular chaperones and connect the chaperone network to protein degradation and cell death pathways. Bcl-2 associated athanogene 5 (BAG5) is a co-chaperone that modulates proteostasis by inhibiting the activity of Heat shock protein 70 (Hsp70) and several E3 ubiquitin ligases, resulting in enhanced neurodegeneration in models of Parkinson’s disease (PD). Here we identify a novel interaction between BAG5 and p62/sequestosome-1 (SQSTM1), suggesting that BAG5 may bridge the chaperone network to autophagy-mediated protein degradation. We found that BAG5 enhanced the formation of pathogenic alpha-synuclein oligomers and regulated the levels and subcellular distribution of p62. These results extend the role of BAG5 in alpha-synuclein processing and intracellular proteostasis.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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