Intraluminal calcium as a primary regulator of endoplasmic reticulum function

The concentration of Ca(2+) inside the lumen of endoplasmic reticulum (ER) regulates a vast array of spatiotemporally distinct cellular processes, from intracellular Ca(2+) signals to intra-ER protein processing and cell death. This review summarises recent data on the mechanisms of luminal Ca(2+)-dependent regulation of Ca(2+) release and uptake as well as ER regulation of cellular adaptive processes. In addition we discuss general biophysical properties of the ER membrane, as trans-endomembrane Ca(2+) fluxes are subject to basic electrical forces, determined by factors such as the membrane potential of the ER and the ease with which Ca(2+) fluxes are able to change this potential (i.e. the resistance of the ER membrane). Although these electrical forces undoubtedly play a fundamental role in shaping [Ca(2+)](ER) dynamics, at present there is very little direct experimental information about the biophysical properties of the ER membrane. Further studies of how intraluminal [Ca(2+)] is regulated, best carried out with direct measurements, are vital for understanding how Ca(2+) orchestrates cell function. Direct monitoring of [Ca(2+)](ER) under conditions where the cytosolic [Ca(2+)] is known may also help to capture elusive biophysical information about the ER, such as the potential difference across the ER membrane. (C) 2005 Elsevier Ltd. All rights reserved.