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

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Listed:
  • Stephan Lange

    (School of Medicine, University of California)

  • Katja Gehmlich

    (BHF Centre of Research Excellence Oxford, University of Oxford)

  • Alexander S. Lun

    (School of Medicine, University of California)

  • Jordan Blondelle

    (School of Medicine, University of California)

  • Charlotte Hooper

    (BHF Centre of Research Excellence Oxford, University of Oxford)

  • Nancy D. Dalton

    (School of Medicine, University of California)

  • Erika A. Alvarez

    (School of Medicine, University of California)

  • Xiaoyu Zhang

    (ACEA Biosciences)

  • Marie-Louise Bang

    (Institute of Genetic and Biomedical Research, UOS Milan, National Research Council
    Humanitas Clinical and Research Center)

  • Yama A. Abassi

    (ACEA Biosciences)

  • Cristobal G. dos Remedios

    (Bosch Institute, University of Sydney)

  • Kirk L. Peterson

    (School of Medicine, University of California)

  • Ju Chen

    (School of Medicine, University of California)

  • Elisabeth Ehler

    (BHF Centre of Research Excellence at King’s College London)

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.

Suggested Citation

  • Stephan Lange & Katja Gehmlich & Alexander S. Lun & Jordan Blondelle & Charlotte Hooper & Nancy D. Dalton & Erika A. Alvarez & Xiaoyu Zhang & Marie-Louise Bang & Yama A. Abassi & Cristobal G. dos Reme, 2016. "MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12120
    DOI: 10.1038/ncomms12120
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