CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes
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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.; Baillie, George S.; Carrier, Lucie; Ehler, Elisabeth; Cuello, Friederike.
In: FEBS J, Vol. 289, No. 15, 2022, p. 4622-4645.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes
AU - Stathopoulou, Konstantina
AU - Schnittger, Josef
AU - Raabe, Janice
AU - Fleischer, Frederic
AU - Mangels, Nils
AU - Piasecki, Angelika
AU - Findlay, Jane
AU - Hartmann, Kristin
AU - Krasemann, Susanne
AU - Schlossarek, Saskia
AU - Uebeler, June
AU - Wixler, Viktor
AU - Blake, Derek J.
AU - Baillie, George S.
AU - Carrier, Lucie
AU - Ehler, Elisabeth
AU - Cuello, Friederike
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16402
U2 - 10.1111/febs.16402
DO - 10.1111/febs.16402
M3 - SCORING: Journal article
VL - 289
SP - 4622
EP - 4645
JO - FEBS J
JF - FEBS J
SN - 1742-464X
IS - 15
ER -
