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

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

Nature communications (2016-06-30)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-α-Actinin (Sarcomeric) antibody produced in mouse, clone EA-53, ascites fluid
Sigma-Aldrich
Anti-Plakoglobin/γ-Catenin antibody produced in goat, affinity isolated antibody, buffered aqueous solution