SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca2+

Bracy Fertig, Jiayue Ling, Edgar E. Nollet, Sara Dobi, Tara Busiau, Kiyotake Ishikawa, Kelly Yamada, Ahyoung Lee, Changwon Kho, Lauren Wills, Amy J. Tibbo, Mark Scott, Kirsten Grant, Kenneth S. Campbell, Emma J. Birks, Niall MacQuaide, Roger Hajjar, Godfrey L. Smith, Jolanda van der Velden, George S. Baillie

Research output: Contribution to journalArticlepeer-review

Abstract

Post-translational modification of the myofilament protein troponin I by phosphorylation is known to trigger functional changes that support enhanced contraction and relaxation of the heart. We report for the first time that human troponin I can also be modified by SUMOylation at lysine 177. Functionally, TnI SUMOylation is not a factor in the development of passive and maximal force generation in response to calcium, however this modification seems to act indirectly by preventing SUMOylation of other myofilament proteins to alter calcium sensitivity and cooperativity of myofilaments. Utilising a novel, custom SUMO site-specific antibody that recognises only the SUMOylated form of troponin I, we verify that this modification occurs in human heart and that it is upregulated during disease.

Original languageEnglish
JournalFEBS Journal
DOIs
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
This work was funded by the BHF PhD studentship programme U.K. to B.F. and G.S.B. BHF Grant FS/15/64/32035. We acknowledge the patients and families of organ donors who donated cardiac samples. Funding: American Heart Association TP135689, NIH HL148785, University of Kentucky Myocardial Recovery Alliance. We thank Dr Gonzalo S. Tejeda for constructing the graphical abstract.

Publisher Copyright:
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Keywords

  • SUMO
  • heart failure
  • myocytes
  • myofilaments
  • troponin I

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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