Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 47, Issue 5, Pages 723-729Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2009.07.014
Keywords
SLN; Sarcolipin; SERCA; Ca2+ ATPase; Phosphorylation; Calcium calmodulin dependent protein kinase II; PLB; Phospholamban
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Funding
- National Institutes of Health [HL-64140]
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Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport. The inhibitory effect of SLN oil cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by beta-adrenergic stimulation. which indicates that SLN is a reversible inhibitor. However the mechanism of this. reversible regulation of SERCA pump by SLN is yet to be determined In the current Study using adult rat ventricular myocytes we provide evidence that the threonine 5 (T5) residue at the N-terminus of SLN which is conserved among various species, critically regulates the SLN function. Point mutation of T5 -> alanine exerts an inhibitory effect on myocyte contractility and calcium transients similar to that of wild-type SLN. whereas mutation of T5 -> glutamic acid which mimics the phosphorylation abolished the inhibitory function of SLN. Our results showed that T5 can be phosphorylated in vitro by calcium-calmodulin dependent protein kinase II (CaMKII) Blocking the CaMKII activity in WT-SLN overexpressing myocytes using autocamtide inhibitory peptide completely abolished the beta-adrenergic response. Taken together, our data suggest that T5 is the key ammo acid which modulates SLN function via phosphorylation/dephosphorylation mechanisms through CaMKII pathway (C) 2009 Elsevier Inc. All rights reserved.
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