ArticleCirculation research2012
Adrenergic signaling controls RGK-dependent trafficking of cardiac voltage-gated L-type Ca2+ channels through PKD1.
Article in Circulation research, 2012. 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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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Mitochondrial CaCommunications biology · 2026Article
- Site-specific genetic and functional signatures of aortic endothelial cells at aneurysm predilection sites in healthy and AngII ApoEAngiogenesis · 2024Article
- SARS-CoV-2-ORF3a variant Q57H reduces its pro-apoptotic activity in host cells.F1000Research · 2024Article
- Cardiac Protein Kinase D1 ablation alters the myocytes β-adrenergic response.Journal of molecular and cellular cardiology · 2023Article
- Sympathetic Nervous System Regulation of Cardiac Calcium Channels.Handbook of experimental pharmacology · 2023Article
- Membrane pools of phosphatidylinositol-4-phosphate regulate KCNQ1/KCNE1 membrane expression.Communications biology · 2021Article
- Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization.Scientific reports · 2019Article
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- Protein kinase D activation induces mitochondrial fragmentation and dysfunction in cardiomyocytes.The Journal of physiology · 2018Article
- Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.Bone · 2017Article
- Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaChannels (Austin, Tex.) · 2016Article
- Isoform-specific dynamic translocation of PKC by α1-adrenoceptor stimulation in live cells.Biochemical and biophysical research communications · 2015Article
- Rem uncouples excitation-contraction coupling in adult skeletal muscle fibers.The Journal of general physiology · 2015Article
- RGK regulation of voltage-gated calcium channels.Science China. Life sciences · 2015Review
- Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2-dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter.Antioxidants & redox signaling · 2014Article
- Differential effects of RGK proteins on L-type channel function in adult mouse skeletal muscle.Biophysical journal · 2014Article
- Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient mice.PloS one · 2014Article
- Rad GTPase deletion increases L-type calcium channel current leading to increased cardiac contraction.Journal of the American Heart Association · 2013Article
- Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts.American journal of physiology. Heart and circulatory physiology · 2013Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThe Rad-Gem/Kir-related family (RGKs) consists of small GTP-binding proteins that strongly inhibit the activity of voltage-gated calcium channels. Among RGKs, Rem1 is strongly and specifically expressed in cardiac tissue. However, the physiological role and regulation of RGKs, and Rem1 in particular, are largely unknown.
objectiveTo determine if Rem1 function is physiologically regulated by adrenergic signaling and thus impacts voltage-gated L-type calcium channel (VLCC) activity in the heart. METHODS AND
resultsWe found that activation of protein kinase D1, a protein kinase downstream of α(1)-adrenergic signaling, leads to direct phosphorylation of Rem1 at Ser18. This results in an increase of the channel activity and plasma membrane expression observed by using a combination of electrophysiology, live cell confocal microscopy, and immunohistochemistry in heterologous expression system and neonatal cardiomyocytes. In addition, we show that stimulation of α(1)-adrenergic receptor-protein kinase D1-Rem1 signaling increases transverse-tubule VLCC expression that results in increased L-type Ca(2+) current density in adult ventricular myocytes.
conclusionThe α(1)-adrenergic stimulation releases Rem1 inhibition of VLCCs through direct phosphorylation of Rem1 at Ser18 by protein kinase D1, resulting in an increase of the channel activity and transverse-tubule expression. Our results uncover a novel molecular regulatory mechanism of VLCC trafficking and function in the heart and provide the first demonstration of physiological regulation of RGK function.
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