Myocyte remodeling in response to hypertrophic stimuli requires nucleocytoplasmic shuttling of muscle LIM protein. J Mol Cell Cardiol 2009 Oct;47(4):426-35
Date
04/21/2009Pubmed ID
19376126Pubmed Central ID
PMC2739242DOI
10.1016/j.yjmcc.2009.04.006Scopus ID
2-s2.0-69249246979 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
CSRP3 or muscle LIM protein (MLP) is a nucleocytoplasmic shuttling protein and a mechanosensor in cardiac myocytes. MLP regulation and function was studied in cultured neonatal rat myocytes treated with pharmacological or mechanical stimuli. Either verapamil or BDM decreased nuclear MLP while phenylephrine and cyclic strain increased it. These results suggest that myocyte contractility regulates MLP subcellular localization. When RNA polymerase II was inhibited with alpha-amanitin, nuclear MLP was reduced by 30%. However, when both RNA polymerase I and II were inhibited with actinomycin D, there was a 90% decrease in nuclear MLP suggesting that its nuclear translocation is regulated by both nuclear and nucleolar transcriptional activity. Using cell permeable synthetic peptides containing the putative nuclear localization signal (NLS) of MLP, nuclear import of the protein in cultured rat neonatal myocytes was inhibited. The NLS of MLP also localizes to the nucleolus. Inhibition of nuclear translocation prevented the increased protein accumulation in response to phenylephrine. Furthermore, cyclic strain of myocytes after prior NLS treatment to remove nuclear MLP resulted in disarrayed sarcomeres. Increased protein synthesis and brain natriuretic peptide expression were also prevented suggesting that MLP is required for remodeling of the myofilaments and gene expression. These findings suggest that nucleocytoplasmic shuttling MLP plays an important role in the regulation of the myocyte remodeling and hypertrophy and is required for adaptation to hypertrophic stimuli.
Author List
Boateng SY, Senyo SE, Qi L, Goldspink PH, Russell BMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Animals, Newborn
Cell Nucleus
Cells, Cultured
Hypertrophy
LIM Domain Proteins
Molecular Sequence Data
Muscle Proteins
Myocardial Contraction
Myocytes, Cardiac
Nuclear Localization Signals
Peptides
Protein Transport
Rats
Rats, Sprague-Dawley
Stress, Mechanical
Subcellular Fractions
Transcription, Genetic
