Calreticulin-Dependent Signaling During Embryonic Development
Ca2+ ions are signaling molecules responsible for controlling developmental processes, including fertilization, differentiation, proliferation, and transcription factor activation. Various cellular functions are regulated by changes in cytoplasmic Ca2+, i
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Calreticulin-Dependent Signaling During Embryonic Development
J. Groenendyk . M. Michalak
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534 2 Calreticulin, a Ca2+-Buffering Chaperone of the ER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 3 Calreticulin Outside the ER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536 4 Impaired Cardiogenesis in the Absence of Calreticulin (Loss-of-Function) . . . . . . . . . . . . . . . . . . . . . . 536 5 Calreticulin Signals Upstream of Calcineurin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536 6 Calreticulin and Ca2+-Dependent Modulation of Transcriptional Pathways during Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538 7 Gain-of-Function of Calreticulin and Embryogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539 8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540
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2009 Springer Science+Business Media, LLC.
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Calreticulin-dependent signaling during embryonic development
Abstract: Ca2+ ions are signaling molecules responsible for controlling developmental processes, including fertilization, differentiation, proliferation, and transcription factor activation. Various cellular functions are regulated by changes in cytoplasmic Ca2+, including gene transcription and expression, protein synthesis, modification, folding and secretion, cell motility, cytoplasmic and mitochondrial energy metabolism, cell cycle progression, and apoptosis. Endoplasmic reticulum is an important Ca2+ storage organelle involved in virtually every aspect of Ca2+ homeostasis. Endoplasmic reticulum luminal Ca2+-binding chaperones such as calreticulin are critical for buffering endoplasmic reticulum Ca2+. In mice, calreticulin deficiency is lethal in utero because of the compromised Ca2+ storage capacity in the endoplasmic reticulum and disrupted InsP3 receptor-mediated Ca2+ release. A disturbance in Ca2+ release results in impaired cardiac development due to inhibited Ca2+-dependent transcriptional pathways. Calreticulin and the endoplasmic reticulum are the key upstream elements for calcineurin in Ca2+-signaling pathways. In contrast upregulation of calreticulin and overloading endoplasmic reticulum with Ca2+ leads to cardiac arrhythmias and impaired development of the cardiac conductive system. List of Abbreviations: DAG, diacylglycerol; HDAC, histone deacetylases; LRP1/CD91, LDL-receptor related protein; MEF2C, myocyte enhancer
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