The endoplasmic reticulum: a multifunctional signaling organelle.
The endoplasmic reticulum (ER) is a multifunctional signaling organelle that controls a wide range of cellular processes such as the entry and release of Ca(2+), sterol biosynthesis, apoptosis and the release of arachidonic acid (AA). One of its primary functions is as a source of the Ca(2+) signals that are released through either inositol 1,4,5-trisphosphate (InsP(3)) or ryanodine receptors (RYRs). Since these receptors are Ca(2+)-sensitive, the ER functions as an excitable system capable of spreading signals throughout the cell through a process of Ca(2+)-induced Ca(2+) release (CICR). This regenerative capacity is particularly important in the control of muscle cells and neurons. Its role as an internal reservoir of Ca(2+) must be accommodated with its other major role in protein synthesis where a constant luminal level of Ca(2+) is essential for protein folding. The ER has a number of stress signaling pathways that activate various transcriptional cascades that regulate the luminal content of the Ca(2+)-dependent chaperones responsible for the folding and packaging of secretory proteins.Another emerging function of the ER is to regulate apoptosis by operating in tandem with mitochondria. Anti-apoptotic regulators of apoptosis such as Bcl-2 may act by reducing the ebb and flow of Ca(2+) through the ER/mitochondrial couple. Conversely, the presenilins that appear to increase the Ca(2+) content of the ER lumen make cells more susceptible to apoptosis.
Berridge
Michael J
MJ
Laboratory of Molecular Signaling, The Babraham Institute, Cambridge CB2 4AT, Babraham, UK. michael.berridge@bbsrc.ac.uk
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology; D009474:Neurons / Q000502:physiology; D015388:Organelles / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology