CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes

Stathopoulou, K. et al. (2022) CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes. FEBS Journal, 289(15), pp. 4622-4645. (doi: 10.1111/febs.16402) (PMID:35176204)

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: Articles
• Additional Information: The project was supported by the Deutsche Stiftung für Herzforschung (grant F/40/17), the Deutsches Zentrum für Herz-Kreislauf Forschung, the Deutsche Forschungsgemeinschaft (DFG CU 53/5-1). J.R. was supported by a fellowship of the Studienstiftung des deutschen Volkes. Work in the Ehler laboratory is funded by the British Heart Foundation and by the Medical Research Council (MR/R017050/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Findlay, Mrs Jane and Baillie, Professor George
• Authors: Stathopoulou, K., Schnittger, J., Raabe, J., Fleischer, F., Mangels, N., Piasecki, A., Findlay, J., Hartmann, K., Krasemann, S., Schlossarek, S., Uebeler, J., Wixler, V., Blake, D. J., Baillie, G., Carrier, L., Ehler, E., and Cuello, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: FEBS Journal
• Publisher: Wiley
• ISSN: 1742-464X
• ISSN (Online): 1742-4658
• Published Online: 17 February 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in FEBS Journal 289(15): 4622-4645
• Publisher Policy: Reproduced under a Creative Commons licence