Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ -ATPase2a and phospholamban in the human heart.
The Ca(2+)-binding S100A1 protein displays a specific and high expression level in the human myocardium and is considered to be an important regulator of heart contractility. Diminished protein levels detected in dilated cardiomyopathy possibly contribute to impaired Ca(2+) handling and contractility in heart failure. To elucidate the S100A1 signaling pathway in the human heart, we searched for S100A1 target proteins by applying S100A1-specific affinity chromatography and immunoprecipitation techniques. We detected the formation of a Ca(2+)-dependent complex of S100A1 with SERCA2a and PLB in the human myocardium. Using confocal laser scanning microscopy, we showed that all three proteins co-localize at the level of the SR in primary mouse cardiomyocytes and confirmed these results by immunoelectron microscopy in human biopsies. Our results support a regulatory role of S100A1 in the contraction-relaxation cycle in the human heart.
Kiewitz
Roland
R
Department of Pediatrics, Division of Clinical Chemistry and Biochemistry, University of Zürich, Steinwiesstr. 75, CH-8032, Zürich, Switzerland.
Acklin
Christian
C
Schäfer
Beat W
BW
Maco
Bohumil
B
Uhrík
Branislav
B
Wuytack
Frank
F
Erne
Paul
P
Heizmann
Claus W
CW
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002478:Cells, Cultured; D002845:Chromatography; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D009418:S100 Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014018:Tissue Distribution; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D009418:S100 Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C110294:S100A1 protein