ArticleNature communications2016
MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 80 citations in OpenAlex.
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- Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy.EMBO molecular medicine · 2025Article
- Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies.Communications biology · 2024Article
- Research progress of ankyrin repeat domain 1 protein: an updated review.Cellular & molecular biology letters · 2024Review
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- Genetic cardiomyopathy and significant systolic heart failure treated with cardiac contractility modulation therapy.Heart rhythm O2 · 2024Article
- The Efficacy of Risk Factor Modification Compared to NADJACC. Basic to translational science · 2024Article
- Exploring Syndecan-4 and MLP and Their Interaction in Primary Cardiomyocytes and H9c2 Cells.Cells · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Structural and signaling proteins in the Z-disk and their role in cardiomyopathies.Frontiers in physiology · 2023Review
- Genetic Ablation ofBiomolecules · 2022Article
- Spatiotemporal transcriptome analysis reveals critical roles for mechano-sensing genes at the border zone in remodeling after myocardial infarction.Nature cardiovascular research · 2022Article
- LIM domain-wide comprehensive virtual mutagenesis provides structural rationale for cardiomyopathy mutations in CSRP3.Scientific reports · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics.Journal of cardiovascular development and disease · 2021Article
- Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- Muscle ankyrin repeat protein 1 (MARP1) locks titin to the sarcomeric thin filament and is a passive force regulator.The Journal of general physiology · 2021Article
- Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.The Journal of clinical investigation · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.