CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes.
Animals
Cardiomyopathy, Hypertrophic
/ metabolism
Intracellular Signaling Peptides and Proteins
/ genetics
LIM-Homeodomain Proteins
/ genetics
Mice
Mice, Knockout
Muscle Proteins
/ genetics
Myocardium
/ metabolism
Myocytes, Cardiac
/ metabolism
Rats
Signal Transduction
Transcription Factors
/ genetics
cardiac myocyte
cardiomyopathy-associated 5
four-and-a-half LIM domains protein 2
hypertrophy
scaffold protein
transcription
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
13
01
2022
received:
23
06
2021
accepted:
15
02
2022
pubmed:
18
2
2022
medline:
5
8
2022
entrez:
17
2
2022
Statut:
ppublish
Résumé
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.
Substances chimiques
Cmya5 protein, mouse
0
Fhl2 protein, mouse
0
Fhl2 protein, rat
0
Intracellular Signaling Peptides and Proteins
0
LIM-Homeodomain Proteins
0
Muscle Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4622-4645Subventions
Organisme : Medical Research Council
ID : G0400153
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R017050/1
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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