CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes

Stathopoulou, Konstantina, Schnittger, Josef, Raabe, Janice, Fleischer, Frederic, Mangels, Nils, Piasecki, Angelika, Findlay, Jane, Hartmann, Kristin, Krasemann, Susanne, Schlossarek, Saskia, Uebeler, June, Wixler, Viktor, Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731, Baillie, George S., Carrier, Lucie, Ehler, Elisabeth and Cuello, Friederike 2022. CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes. FEBS Journal 289 (15) , pp. 4622-4645. 10.1111/febs.16402

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Abstract

Four-and-a-half LIM domains protein 2 (FHL2) is an anti-hypertrophic adaptor protein that regulates cardiac myocyte signalling and function. Herein, we identified cardiomyopathy-associated 5 (CMYA5) as a novel FHL2 interaction partner in cardiac myocytes. In vitro pull-down assays demonstrated interaction between FHL2 and the N- and C-terminal regions of CMYA5. The interaction was verified in adult cardiac myocytes by proximity ligation assays. Immunofluorescence and confocal microscopy demonstrated co-localisation in the same subcellular compartment. The binding interface between FHL2 and CMYA5 was mapped by peptide arrays. Exposure of neonatal rat ventricular myocytes to a CMYA5 peptide covering one of the FHL2 interaction sites led to an increase in cell area at baseline, but a blunted response to chronic phenylephrine treatment. In contrast to wild-type hearts, loss or reduced FHL2 expression in Fhl2-targeted knockout mouse hearts or in a humanised mouse model of hypertrophic cardiomyopathy led to redistribution of CMYA5 into the perinuclear and intercalated disc region. Taken together, our results indicate a direct interaction of the two adaptor proteins FHL2 and CMYA5 in cardiac myocytes, which might impact subcellular compartmentation of CMYA5.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License
Publisher:	Wiley
ISSN:	1742-464X
Date of First Compliant Deposit:	29 March 2022
Date of Acceptance:	11 February 2022
Last Modified:	05 May 2023 23:18
URI:	https://orca.cardiff.ac.uk/id/eprint/148955

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