MLP and CARP Are Linked to Chronic PKCα Signalling in Dilated Cardiomyopathy

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Jun 30

PMID 27353086

Citations 46

Authors

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 Remedios

Kirk L Peterson

Ju Chen

Elisabeth Ehler

Affiliations

Soon will be listed here.

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.

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