ArticleThe Journal of biological chemistry2013
A separate pool of cardiac phospholemman that does not regulate or associate with the sodium pump: multimers of phospholemman in ventricular muscle.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 32 citations in OpenAlex.
- Lipid-induced S-palmitoylation of Insulin-Responsive Aminopeptidase (IRAP) drives the onset of insulin resistance in the heart.Cellular and molecular life sciences : CMLS · 2026Article
- FoxO1-zDHHC4-CD36 S-Acylation Axis Drives Metabolic Dysfunction in Diabetes.Circulation research · 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
- Article
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Phospholemman Phosphorylation Regulates Vascular Tone, Blood Pressure, and Hypertension in Mice and Humans.Circulation · 2021Article
- Sarcolipin alters SERCA1a interdomain communication by impairing binding of both calcium and ATP.Scientific reports · 2021Article
- FXYD protein isoforms differentially modulate human Na/K pump function.The Journal of general physiology · 2020Article
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- Heart failure leads to altered β2-adrenoceptor/cyclic adenosine monophosphate dynamics in the sarcolemmal phospholemman/Na,K ATPase microdomain.Cardiovascular research · 2019Article
- Maleimide scavenging enhances determination of protein S-palmitoylation state in acyl-exchange methods.BioTechniques · 2017Article
- Impaired AQP2 trafficking in Fxyd1 knockout mice: A role for FXYD1 in regulated vesicular transport.PloS one · 2017Article
- L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes.Biochemistry · 2016Article
- BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.Journal of molecular and cellular cardiology · 2016Article
- Protein Phosphatase 1c Associated with the Cardiac Sodium Calcium Exchanger 1 Regulates Its Activity by Dephosphorylating Serine 68-phosphorylated Phospholemman.The Journal of biological chemistry · 2016Article
- FXYD5: Na(+)/K(+)-ATPase Regulator in Health and Disease.Frontiers in cell and developmental biology · 2016Review
- Phospholemman is not required for the acute stimulation of Na⁺-K⁺-ATPase α₂-activity during skeletal muscle fatigue.American journal of physiology. Cell physiology · 2015Article
- Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.The Journal of physiology · 2015Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPhospholemman regulates the plasmalemmal sodium pump in excitable tissues.
resultsIn cardiac muscle, a subpopulation of phospholemman with a unique phosphorylation signature associates with other phospholemman molecules but not with the pump.
conclusionPhospholemman oligomers exist in cardiac muscle. SIGNIFICANCE: Much like phospholamban regulation of SERCA, phospholemman exists as both a sodium pump inhibiting monomer and an unassociated oligomer. Phospholemman (PLM), the principal quantitative sarcolemmal substrate for protein kinases A and C in the heart, regulates the cardiac sodium pump. Much like phospholamban, which regulates the related ATPase SERCA, PLM is reported to oligomerize. We investigated subpopulations of PLM in adult rat ventricular myocytes based on phosphorylation status. Co-immunoprecipitation identified two pools of PLM: one not associated with the sodium pump phosphorylated at Ser(63) and one associated with the pump, both phosphorylated at Ser(68) and unphosphorylated. Phosphorylation of PLM at Ser(63) following activation of PKC did not abrogate association of PLM with the pump, so its failure to associate with the pump was not due to phosphorylation at this site. All pools of PLM co-localized to cell surface caveolin-enriched microdomains with sodium pump α subunits, despite the lack of caveolin-binding motif in PLM. Mass spectrometry analysis of phosphospecific immunoprecipitation reactions revealed no unique protein interactions for Ser(63)-phosphorylated PLM, and cross-linking reagents also failed to identify any partner proteins for this pool. In lysates from hearts of heterozygous transgenic animals expressing wild type and unphosphorylatable PLM, Ser(63)-phosphorylated PLM co-immunoprecipitated unphosphorylatable PLM, confirming the existence of PLM multimers. Dephosphorylation of the PLM multimer does not change sodium pump activity. Hence like phospholamban, PLM exists as a pump-inhibiting monomer and an unassociated oligomer. The distribution of different PLM phosphorylation states to different pools may be explained by their differential proximity to protein phosphatases rather than a direct effect of phosphorylation on PLM association with the pump.
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