Signalling specificity in GPCR-dependent Ca2+ signalling.
Cells use signalling networks to translate with high fidelity extracellular signals into specific cellular functions. Signalling networks are often composed of multiple signalling pathways that act in concert to regulate a particular cellular function. In the centre of the networks are the receptors that receive and transduce the signals. A versatile family of receptors that detect a remarkable variety of signals are the G protein-coupled receptors (GPCRs). Virtually all cells express several GPCRs that use the same biochemical machinery to transduce their signals. Considering the specificity and fidelity of signal transduction, a central question in cell signalling is how signalling specificity is achieved, in particular among GPCRs that use the same biochemical machinery. Ca(2+) signalling is particularly suitable to address such questions, since [Ca(2+)](i) can be recorded with excellent spatial and temporal resolutions in living cells and tissues and now in living animals. Ca(2+) is a unique second messenger in that both biochemical and biophysical components form the Ca(2+) signalling complex to regulate its concentration. Both components act in concert to generate repetitive [Ca(2+)](i) oscillations that can be either localized or in the form of global, propagating Ca(2+) waves. Most of the key proteins that form Ca(2+) signalling complexes are known and their activities are reasonably well understood on the biochemical and biophysical levels. We review here the information gained from studying Ca(2+) signalling by GPCRs to gain further understanding of the mechanisms used to generate cellular signalling specificity.
Kiselyov
Kirill
K
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Shin
Dong Min
DM
Muallem
Shmuel
S
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology*
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins