ArticleProceedings of the National Academy of Sciences of the United States of America2006
Cardiac-specific overexpression of sarcolipin in phospholamban null mice impairs myocyte function that is restored by phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 85 citations in OpenAlex.
- Site-1 protease is a negative regulator of sarcolipin promoter activity.Communications biology · 2025Article
- Cardiac Slc25a49-Mediated Energy Reprogramming Governs Doxorubicin-Induced Cardiomyopathy through the G6P-AP-1-Sln Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glyoxal is a superior fixative to formaldehyde in promoting antigenicity and structural integrity in murine cardiac tissues.Journal of molecular and cellular cardiology plus · 2025Article
- The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.Journal of translational medicine · 2024Article
- The Meeting of Micropeptides with Major CaMembranes · 2023Review
- Calcium cycling as a mediator of thermogenic metabolism in adipose tissue.Molecular pharmacology · 2022Article
- Structure-function relationships and modifications of cardiac sarcoplasmic reticulum Ca2+-transport.Physiological research · 2021Review
- Structural basis for sarcolipin's regulation of muscle thermogenesis by the sarcoplasmic reticulum CaScience advances · 2021Article
- Sarcoplasmic Reticulum from Horse Gluteal Muscle Is Poised for Enhanced Calcium Transport.Veterinary sciences · 2021Article
- Nothing Regular about the Regulins: Distinct Functional Properties of SERCA Transmembrane Peptide Regulatory Subunits.International journal of molecular sciences · 2021Review
- Sarcolipin alters SERCA1a interdomain communication by impairing binding of both calcium and ATP.Scientific reports · 2021Article
- Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.Veterinary sciences · 2020Article
- SERCA2a: a key protein in the CaHeart failure reviews · 2020Review
- Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.The Journal of physiology · 2017Article
- Sarcolipin Promotes Uncoupling of the SERCA CaBiochemistry · 2016Article
- Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?Journal of molecular and cellular cardiology · 2016Review
- Regulation of the sarcoplasmic reticulum calcium pump by divergent phospholamban isoforms in zebrafish.The Journal of biological chemistry · 2015Article
- Cardiac specific expression of threonine 5 to alanine mutant sarcolipin results in structural remodeling and diastolic dysfunction.PloS one · 2015Article
- Endoplasmic reticulum resident protein 44 (ERp44) deficiency in mice and zebrafish leads to cardiac developmental and functional defects.Journal of the American Heart Association · 2014Article
- Muscle structure influences utrophin expression in mdx mice.PLoS genetics · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) by direct binding and is superinhibitory if it binds as a binary complex with phospholamban (PLN). To demonstrate whether overexpression of SLN in the heart might impair cardiac function directly, transgenic (TG) mice with cardiac-specific overexpression of NF-SLN (SLN tagged at its N terminus with the FLAG epitope) were generated on a phospholamban (PLN) null (PLN KO) background. In NF-SLN TG/PLN KO cardiac microsomes, the apparent affinity of SERCA2a for Ca2+ was decreased compared with non-TG littermate PLN KO hearts. Analyses of isolated NF-SLN/PLN KO cardiomyocytes revealed impaired cardiac contractility, reduced calcium transient peak amplitude, and slower decay kinetics compared to PLN KO animals. In these cardiomyocytes, isoproterenol restored calcium dynamics to the levels seen in PLN KO. Invasive hemodynamic and echocardiographic analyses of NF-SLN/PLN KO mouse cardiac muscle in vivo showed no direct effects of NF-SLN overexpression when compared to PLN KO mice. A possible mechanism for the lack of effects in the whole heart may be a responsiveness to phosphorylation because we determined that NF-SLN can be phosphorylated in cardiomyocytes in response to isoproterenol, and we provide evidence that serine/threonine kinase 16 is a kinase that can phosphorylate NF-SLN. Site-directed mutagenesis showed that SLN Thr-5 is the target site for this kinase. These data show that overexpression of NF-SLN can inhibit SERCA2a in the absence of PLN and that the inhibition of SERCA2a is correlated with impairment of contractility and calcium cycling in cardiomyocytes.
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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.