Calreticulin in cardiac development and pathology.
Calreticulin is a Ca(2+) binding/storage chaperone resident in the lumen of endoplasmic reticulum (ER). The protein is an important component of the calreticulin/calnexin cycle and the quality control pathways in the ER. In mice, calreticulin deficiency is lethal due to impaired cardiac development. This is not surprising because the protein is expressed at high level at early stages of cardiac development. Overexpression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Recent studies on calreticulin-deficient and transgenic mice revealed that the protein is a key upstream regulator of calcineurin-dependent pathways during cardiac development. Calreticulin and ER may play important role in cardiac development and postnatal pathologies.
Michalak
Marek
M
Canadian Institutes of Health Research Membrane Protein Research Group and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Lynch
Jeffrey
J
Groenendyk
Jody
J
Guo
Lei
L
Robert Parker
J M
JM
Opas
Michal
M
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D037282:Calreticulin / Q000737:chemistry / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D006321:Heart / Q000196:embryology*; D006327:Heart Block / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic
D037282:Calreticulin; D019703:Calcineurin; D002118:Calcium