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Published on: November 13, 2015
CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes
Francesca Rusconi1, Hrishikesh Thakur, Jinliang Li
1Interdisciplinary Stem Cell Institute, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Insights
The scaffold protein CIP4 (JNK-interacting protein 4) is crucial for cardiac myocyte growth. Inhibiting CIP4 prevents cardiac hypertrophy, suggesting its role in heart disease signaling.
Area of Science:
- Cell Biology
- Cardiovascular Research
- Molecular Signaling
Background:
- CIP4 (JNK-interacting protein 4) is a scaffold protein involved in membrane dynamics and cytoskeleton organization.
- CIP4 is expressed in the heart, but its function in cardiac myocytes remains uncharacterized.
Purpose of the Study:
- To investigate the role of CIP4 in cardiac myocyte growth and hypertrophy.
- To determine if CIP4 is involved in the signaling pathways that regulate cardiac myocyte size.
Main Methods:
- RNA interference (RNAi) was used to reduce CIP4 expression in neonatal rat ventricular myocytes.
- Hypertrophic stimuli included phenylephrine, leukemia inhibitor factor, and fetal bovine serum.
- Cardiac myocyte hypertrophy was assessed by morphometry, atrial natriuretic factor expression, and protein synthesis measurements.
Main Results:
- CIP4 expression is required for hypertrophic growth induced by various stimuli.
- CIP4 expression is upregulated by hypertrophic stimulation.
- Inhibition of CIP4 by siRNA blocked hypertrophy, which was rescued by wild-type CIP4 but not a mutant lacking the FCH domain.
Conclusions:
- CIP4 plays a significant role in the intracellular signaling network controlling cardiac myocyte growth.
- CIP4 is a key regulator of cardiac hypertrophy, suggesting its involvement in heart disease pathogenesis.
Background:
CIP4 is a scaffold protein that regulates membrane deformation and tubulation, organization of the actin cytoskeleton, endocytosis of growth factor receptors, and vesicle trafficking. Although expressed in the heart, CIP4 has not been studied with regards to its potential function in cardiac myocytes.
Results:
We now show using RNA interference that CIP4 expression in neonatal rat ventricular myocytes is required for the induction of non-mitotic, hypertrophic growth by the α-adrenergic agonist phenylephrine, the IL-6 cytokine leukemia inhibitor factor, and fetal bovine serum, as assayed using morphometry, immunocytochemistry for the hypertrophic marker atrial natriuretic factor and [3H]leucine incorporation for de novo protein synthesis. This requirement was consistent with the induction of CIP4 expression by hypertrophic stimulation. The inhibition of myocyte hypertrophy by CIP4 small interfering oligonucleotides (siRNA) was rescued by expression of a recombinant CIP4 protein, but not by a mutant lacking the N-terminal FCH domain responsible for CIP4 intracellular localization.
Conclusions:
These results imply that CIP4 plays a significant role in the intracellular hypertrophic signal transduction network that controls the growth of cardiac myocytes in heart disease.
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