Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes

Judith Krysiak, Andreas Unger, Lisa Beckendorf, Nazha Hamdani, Marion Frieling-Salewsky, Margaret M. Redfield, Cris G. Remedios, Farah Sheikh, Ulrich Gergs, Peter Boknik and Wolfgang A. Linke ()
Additional contact information
Judith Krysiak: Ruhr University Bochum
Andreas Unger: Ruhr University Bochum
Lisa Beckendorf: Ruhr University Bochum
Nazha Hamdani: Ruhr University Bochum
Marion Frieling-Salewsky: University of Muenster
Margaret M. Redfield: Division of Cardiovascular Diseases, Mayo Clinic
Cris G. Remedios: University of Sydney
Farah Sheikh: University of California-San Diego
Ulrich Gergs: University of Halle-Wittenberg
Peter Boknik: University of Muenster
Wolfgang A. Linke: University of Muenster

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks mitogen-activated protein-kinase signaling in this complex. Our work establishes PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which regulates titin properties and kinase signaling at the myofilaments.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02483-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02483-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02483-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().