The endoplasmic reticulum and junctional membrane communication during calcium signaling

The endoplasmic reticulum is a major organelle in all eukaryotic cells which performs multiple functions including protein and lipid synthesis and sorting, drug metabolism, and Ca(2+) storage and release. The endoplasmic reticulum, and its specialized muscle counterpart the sarcoplasmic reticulum, is the largest and most extensive of Ca(2+) storage organelle in eukaryotic cells, often occupying in excess of 10% of the cell volume. There are three major components of Ca(2+) storage organelles which mediate their major functions: Ca(2+) uptake, mediated by pumps and exchangers; storage enhanced by luminal Ca(2+) binding proteins, and Ca(2+) mobilization mediated by specific ion channels. Ca(2+) mobilization from the endoplasmic reticulum plays a central role in Ca(2+) signaling. Through Ca(2+) release channels in its membrane, the pervading and plastic structure of the endoplasmic reticulum allows Ca(2+) release to be rapidly targeted to specific cytoplasmic sites across the whole cell. That several endoplasmic reticulum Ca(2+) release channels are also activated by Ca(2+) itself, contributes to endoplasmic reticulum membrane excitability which is the principal basis for generating spatio-temporal complex cellular Ca(2+) signals, allowing specific processes to be regulated by this universal messenger. In addition, the endoplasmic reticulum forms discrete junctions with the plasma membrane and membranes of organelles such as mitochondria and lysosomes, forming nanodomains at their interfaces that play critical roles in Ca(2+) signaling during key cellular processes such as cellular bioenergetics, apoptosis and autophagy. At these junctions key Ca(2+) transport and regulatory processes come into play, and a recurring theme in this review is the often tortuous paths in identifying these mechanisms unequivocally. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.