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

doi:10.1111/febs.16537

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 journal › Article › peer-review

4 Scopus citations

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 language	English
Pages (from-to)	6267-6285
Number of pages	19
Journal	FEBS Journal
Volume	289
Issue number	20
DOIs	https://doi.org/10.1111/febs.16537
State	Published - Oct 2022

Bibliographical note

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

Funding

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. 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.

Funders	Funder number
University of Kentucky Myocardial Recovery Alliance
National Institutes of Health (NIH)	HL148785
National Heart, Lung, and Blood Institute (NHLBI)	R01HL149164
American the American Heart Association	TP135689
British Heart Foundation	FS/15/64/32035

Keywords

SUMO
heart failure
myocytes
myofilaments
troponin I

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/febs.16537

Cite this

Fertig, B., Ling, J., Nollet, E. E., Dobi, S., Busiau, T., Ishikawa, K., Yamada, K., Lee, A., Kho, C., Wills, L., Tibbo, A. J., Scott, M., Grant, K., Campbell, K. S., Birks, E. J., MacQuaide, N., Hajjar, R., Smith, G. L., van der Velden, J., & Baillie, G. S. (2022). SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca²⁺. FEBS Journal, 289(20), 6267-6285. https://doi.org/10.1111/febs.16537

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.",

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Fertig, B, Ling, J, Nollet, EE, Dobi, S, Busiau, T, Ishikawa, K, Yamada, K, Lee, A, Kho, C, Wills, L, Tibbo, AJ, Scott, M, Grant, K, Campbell, KS , Birks, EJ, MacQuaide, N, Hajjar, R, Smith, GL, van der Velden, J & Baillie, GS 2022, 'SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca²⁺', FEBS Journal, vol. 289, no. 20, pp. 6267-6285. https://doi.org/10.1111/febs.16537

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AU - Scott, Mark

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