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 Ca2+, sterol biosynthesis, apoptosis and the release of arachidonic acid (AA). One of its primary functions is as a source of the Ca2+ signals that are released through either inositol 1,4,5-trisphosphate (InsP(3)) or ryanodine receptors (RYRs). Since these receptors are Ca2+-sensitive, the ER functions as an excitable system capable of spreading signals throughout the cell through a process of Ca2+-induced Ca2+ release (CICR). This regenerative capacity is particularly important in the control of muscle cells and neurons. Its role as an internal reservoir of Ca2+ must be accommodated with its other major role in protein synthesis where a constant luminal level of Ca2+ 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 Ca2+-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 Ca2+ through the ER/mitochondrial couple. Conversely, the presenilins that appear to increase the Ca2+ content of the ER lumen make cells more susceptible to apoptosis. (C) 2002 Elsevier Science Ltd. All rights reserved.