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Sci. STKE, 16 April 2002
Vol. 2002, Issue 128, p. tw145
[DOI: 10.1126/stke.2002.128.tw145]

EDITORS' CHOICE

Cell Biology Specificity Through Localization

It has been a bit of a puzzle how it is that B2 bradykinin receptors (B2Rs) and M1 muscarinic receptors (M1AChRs) can both be coupled to activation of phospholipase C, which catalyzes cleavage of phosphatidylinositol bisphosphate into diacyl glycerol (DAG, an activator of protein kinase C family members) and inositol-1,4,5-trisphosphate (IP3, which acts through a receptor to release calcium from intracellular stores), yet only stimulation of B2Rs can actually increase intracellular concentrations of free calcium. To get at this problem, Delmas et al. developed a method to use mammalian homologs of Trp (transient receptor potential) channels from Drosophila as sensors that function in real time to measure intracellular concentrations of DAG and IP3 produced in response to cell stimulation. They found that activation of either B2Rs or M1AchRs caused accumulation of DAG and IP3. The exclusive coupling of the B2R to calcium release appeared to be the result of proximity of the B2Rs to IP3Rs. Close association of those receptors was demonstrated by their presence together in microvesicles and by their coimmunoprecipitation from transfected cells. The association appears to require the actin cytoskeleton, as it was disrupted in the presence of cyotcholasin D. It seems that only when the IP3Rs are close to the activating receptor (B2R, in this case) do concentrations of IP3 get high enough fast enough to cause calcium mobilization. The authors point out that we are left wondering what the purpose of the IP3 that is generated by activated M1AchRs might be.

P. Delmas, N. Wanaverbecq, F. C. Abogadie, M. Mistry, D. A. Brown, Signaling microdomains define the specificity of receptor-mediated InsP3 pathways in neurons. Neuron 14, 209-220 (2002). [Online Journal]

Citation: Specificity Through Localization. Sci. STKE 2002, tw145 (2002).


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