MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

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MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy. / Lange, Stephan; Gehmlich, Katja; Lun, Alexander S.; Blondelle, Jordan; Hooper, Charlotte; Dalton, Nancy D.; Alvarez, Erika A.; Zhang, Xiaoyu; Bang, Marie-Louise; Abassi, Yama A.; Dos Remedios, Cristobal G.; Peterson, Kirk L.; Chen, Ju; Ehler, Elisabeth.

In: Nature Communications, Vol. 7, No. 1, 12120, 01.11.2016.

Research output: Contribution to journalArticlepeer-review

Harvard

Lange, S, Gehmlich, K, Lun, AS, Blondelle, J, Hooper, C, Dalton, ND, Alvarez, EA, Zhang, X, Bang, M-L, Abassi, YA, Dos Remedios, CG, Peterson, KL, Chen, J & Ehler, E 2016, 'MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy', Nature Communications, vol. 7, no. 1, 12120. https://doi.org/10.1038/ncomms12120

APA

Lange, S., Gehmlich, K., Lun, A. S., Blondelle, J., Hooper, C., Dalton, N. D., Alvarez, E. A., Zhang, X., Bang, M-L., Abassi, Y. A., Dos Remedios, C. G., Peterson, K. L., Chen, J., & Ehler, E. (2016). MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy. Nature Communications, 7(1), [12120]. https://doi.org/10.1038/ncomms12120

Vancouver

Author

Lange, Stephan ; Gehmlich, Katja ; Lun, Alexander S. ; Blondelle, Jordan ; Hooper, Charlotte ; Dalton, Nancy D. ; Alvarez, Erika A. ; Zhang, Xiaoyu ; Bang, Marie-Louise ; Abassi, Yama A. ; Dos Remedios, Cristobal G. ; Peterson, Kirk L. ; Chen, Ju ; Ehler, Elisabeth. / MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy. In: Nature Communications. 2016 ; Vol. 7, No. 1.

Bibtex

@article{f120a6bf246f4ebda67f025fa2a6025b,
title = "MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy",
abstract = "MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.",
keywords = "Animals, COS Cells, Cardiomyopathy, Dilated/metabolism, Cell Line, Cercopithecus aethiops, Escherichia coli, Gene Expression Regulation, Heart Failure/etiology, Humans, LIM Domain Proteins/genetics, Male, Mice, Muscle Proteins/genetics, Nuclear Proteins/genetics, Protein Kinase C-alpha/genetics, Repressor Proteins/genetics, Signal Transduction",
author = "Stephan Lange and Katja Gehmlich and Lun, {Alexander S.} and Jordan Blondelle and Charlotte Hooper and Dalton, {Nancy D.} and Alvarez, {Erika A.} and Xiaoyu Zhang and Marie-Louise Bang and Abassi, {Yama A.} and {Dos Remedios}, {Cristobal G.} and Peterson, {Kirk L.} and Ju Chen and Elisabeth Ehler",
year = "2016",
month = nov,
day = "1",
doi = "10.1038/ncomms12120",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

AU - Lange, Stephan

AU - Gehmlich, Katja

AU - Lun, Alexander S.

AU - Blondelle, Jordan

AU - Hooper, Charlotte

AU - Dalton, Nancy D.

AU - Alvarez, Erika A.

AU - Zhang, Xiaoyu

AU - Bang, Marie-Louise

AU - Abassi, Yama A.

AU - Dos Remedios, Cristobal G.

AU - Peterson, Kirk L.

AU - Chen, Ju

AU - Ehler, Elisabeth

PY - 2016/11/1

Y1 - 2016/11/1

N2 - MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.

AB - MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.

KW - Animals

KW - COS Cells

KW - Cardiomyopathy, Dilated/metabolism

KW - Cell Line

KW - Cercopithecus aethiops

KW - Escherichia coli

KW - Gene Expression Regulation

KW - Heart Failure/etiology

KW - Humans

KW - LIM Domain Proteins/genetics

KW - Male

KW - Mice

KW - Muscle Proteins/genetics

KW - Nuclear Proteins/genetics

KW - Protein Kinase C-alpha/genetics

KW - Repressor Proteins/genetics

KW - Signal Transduction

U2 - 10.1038/ncomms12120

DO - 10.1038/ncomms12120

M3 - Article

C2 - 27353086

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 12120

ER -