Intraluminal calcium as a primary regulator of endoplasmic reticulum function.
The concentration of Ca2+ inside the lumen of endoplasmic reticulum (ER) regulates a vast array of spatiotemporally distinct cellular processes, from intracellular Ca2+ signals to intra-ER protein processing and cell death. This review summarises recent data on the mechanisms of luminal Ca2+-dependent regulation of Ca2+ 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 Ca2+ fluxes are subject to basic electrical forces, determined by factors such as the membrane potential of the ER and the ease with which Ca2+ 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 [Ca2+](ER) dynamics, at present there is very little direct experimental information about the biophysical properties of the ER membrane. Further studies of how intraluminal [Ca2+] is regulated, best carried out with direct measurements, are vital for understanding how Ca2+ orchestrates cell function. Direct monitoring of [Ca2+](ER) under conditions where the cytosolic [Ca2+] is known may also help to capture elusive biophysical information about the ER, such as the potential difference across the ER membrane.
Burdakov
Denis
D
Faculty of Life Sciences, The University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Petersen
Ole H
OH
Verkhratsky
Alexei
A
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D002118:Calcium