Assembling pieces of the cardiac puzzle; calreticulin and calcium-dependent pathways in cardiac development, health, and disease.
Calreticulin is a Ca(2+)-binding chaperone of the sarcoplasmic/endoplasmic reticulum. It is an important Ca(2+) buffer, a regulator of Ca(2+) homeostasis, and a component of protein quality control processes in the secretory pathway. Calreticulin is essential for cardiac development; its gene is tightly regulated during cardiogenesis, and in the absence of calreticulin, cardiac development is impaired. The protein is highly expressed in the developing heart and down-regulated after birth in the healthy mature heart. Overexpression of calreticulin in postnatal heart leads to bradyarrhythima and complete heart block, followed by sudden death. The calreticulin gene is a target of transcription factors involved in fetal cardiac program (Nkx2.5, myocardin, myocyte enhancer factor 2C, and GATA6). Calreticulin works upstream of calcineurin and myocyte enhancer factor 2C in a Ca(2+)-dependent signal transduction cascade linking the endoplasmic reticulum and the nucleus during cardiac development.
Membrane Protein Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Jeffrey M
JM
Lynch
Kaari
K
Chilibeck
Yuanyuan
Y
Qui
Marek
M
Michalak
D000818:Animals; D001919:Bradycardia / Q000209:etiology*; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D037282:Calreticulin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006327:Heart Block / Q000209:etiology*; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D014158:Transcription, Genetic
D037282:Calreticulin; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D019703:Calcineurin; D002118:Calcium