Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing
Pohl GM, Göz M, Gaertner A, Brodehl A, Cimen T, Saguner AM, Schulze-Bahr E, Walhorn V, Anselmetti D, Milting H (2023)
Frontiers in Cardiovascular Medicine 10: 1127261.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Pohl, Greta Marie;
Göz, ManuelUniBi;
Gaertner, Anna;
Brodehl, Andreas;
Cimen, Tolga;
Saguner, Ardan M.;
Schulze-Bahr, Eric;
Walhorn, VolkerUniBi ;
Anselmetti, DarioUniBi ;
Milting, Hendrik
Abstract / Bemerkung
BackgroundArrhythmogenic cardiomyopathy can be caused by genetic variants in desmosomal cadherins. Since cardiac desmosomal cadherins are crucial for cell-cell-adhesion, their correct localization at the plasma membrane is essential.MethodsNine desmocollin-2 variants at five positions from various public genetic databases (p.D30N, p.V52A/I, p.G77V/D/S, p.V79G, p.I96V/T) and three additional conserved positions (p.C32, p.C57, p.F71) within the prodomain were investigated in vitro using confocal microscopy. Model variants (p.C32A/S, p.V52G/L, p.C57A/S, p.F71Y/A/S, p.V79A/I/L, p.I96l/A) were generated to investigate the impact of specific amino acids. ResultsWe revealed that all analyzed positions in the prodomain are critical for the intracellular transport. However, the variants p.D30N, p.V52A/I and p.I96V listed in genetic databases do not disturb the intracellular transport revealing that the loss of these canonical sequences may be compensated.ConclusionAs disease-related homozygous truncating desmocollin-2 variants lacking the transmembrane domain are not localized at the plasma membrane, we predict that some of the investigated prodomain variants may be relevant in the context of arrhythmogenic cardiomyopathy due to disturbed intracellular transport.
Stichworte
desmosome;
desmocollin-2;
DSC2;
prodomain;
signal peptide;
genetic;
variants;
intracellular transport;
arrhythmogenic cardiomyopathy
Erscheinungsjahr
2023
Zeitschriftentitel
Frontiers in Cardiovascular Medicine
Band
10
Art.-Nr.
1127261
Urheberrecht / Lizenzen
eISSN
2297-055X
Page URI
https://pub.uni-bielefeld.de/record/2980017
Zitieren
Pohl GM, Göz M, Gaertner A, et al. Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing. Frontiers in Cardiovascular Medicine . 2023;10: 1127261.
Pohl, G. M., Göz, M., Gaertner, A., Brodehl, A., Cimen, T., Saguner, A. M., Schulze-Bahr, E., et al. (2023). Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing. Frontiers in Cardiovascular Medicine , 10, 1127261. https://doi.org/10.3389/fcvm.2023.1127261
Pohl, Greta Marie, Göz, Manuel, Gaertner, Anna, Brodehl, Andreas, Cimen, Tolga, Saguner, Ardan M., Schulze-Bahr, Eric, Walhorn, Volker, Anselmetti, Dario, and Milting, Hendrik. 2023. “Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing”. Frontiers in Cardiovascular Medicine 10: 1127261.
Pohl, G. M., Göz, M., Gaertner, A., Brodehl, A., Cimen, T., Saguner, A. M., Schulze-Bahr, E., Walhorn, V., Anselmetti, D., and Milting, H. (2023). Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing. Frontiers in Cardiovascular Medicine 10:1127261.
Pohl, G.M., et al., 2023. Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing. Frontiers in Cardiovascular Medicine , 10: 1127261.
G.M. Pohl, et al., “Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing”, Frontiers in Cardiovascular Medicine , vol. 10, 2023, : 1127261.
Pohl, G.M., Göz, M., Gaertner, A., Brodehl, A., Cimen, T., Saguner, A.M., Schulze-Bahr, E., Walhorn, V., Anselmetti, D., Milting, H.: Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing. Frontiers in Cardiovascular Medicine . 10, : 1127261 (2023).
Pohl, Greta Marie, Göz, Manuel, Gaertner, Anna, Brodehl, Andreas, Cimen, Tolga, Saguner, Ardan M., Schulze-Bahr, Eric, Walhorn, Volker, Anselmetti, Dario, and Milting, Hendrik. “Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing”. Frontiers in Cardiovascular Medicine 10 (2023): 1127261.
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