"Kissin' cousins": intimate plasma membrane-ER interactions underlie capacitative calcium entry

• Published in: Cell 1999-10, Vol.99 (1), p.5-8
• Main Author: Putney, Jr, J W
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport; Calcium - metabolism; Cell Membrane - metabolism; Electric Conductivity; Endoplasmic Reticulum - metabolism; Eukaryotic Cells - metabolism
• ISSN: 0092-8674
• DOI: 10.1016/S0092-8674(00)80056-2

Ligand-induced generation of intracellular calcium ([Ca super(2+)] sub(i)) signals in nonexcitable cells involves activation of phospholipase C and generation of the Ca super(2+)-mobilizlng messenger, inositol 1,4,5-trisphosphate (IP sub(3)). IP sub(3) acts by binding to a specific receptor-ion channel on the endoplasmic reticulum (ER) activating the Ca super(2+)-permeable channel and thus causing the release of stored Ca super(2+) to the cytoplasm. This release of Ca super(2+) is closely followed by an influx of Ca super(2+) into the cell across the plasma membrane (PM). The signal for activation of the PM channels does not come from the receptors or their associated G proteins, nor from IP sub(3), but appears to be a consequence of the fall of Ca super(2+) within the ER Ca super(2+) stores. Thus, the initial steps in the pathway can be bypassed and Ca super(2+) can be discharged passively by any of several experimental strategies. These include inhibition of the ATP-dependent Ca super(2+) pumps in the ER or buffering [Ca super(2+)] sub(i) to very low levels, thus preventing uptake into the ER, or application of Ca super(2+) ionophores that directly transport Ca super(2+) out of the ER. In each case, the depletion of Ca super(2+) appears capable of activating the Ca super(2+) entry pathway and to the full extent possible with the more physiological, IP sub(3)-mediated mechanism. This process is called "capacitative calcium entry" or "store-operated calcium entry." In recent years there has been considerable interest and speculation regarding the nature of the channels and the mechanism linking the depletion of intracellular Ca super(2+) stores to the activation of this important Ca super(2+) entry pathway.