Trends in Neurosciences
Functional organization of PLC signaling microdomains in neurons
Section snippets
PLC-mediated signaling to TRP channels: an example of receptor–ion-channel segregation
The sophistication of PLC signaling is best illustrated by the phototransduction cascade in the fruitfly Drosophila 3, 4, 5. This PLCβ-coupled mechanism represents the fastest Gq-protein-signaling pathway known: the absorption of a single photon by rhodopsin is translated into a physiological response (a depolarization) in just 20 ms [6]. Nonetheless, phototransduction in flies is a complex, multiprotein cascade involving many enzymatic processes. First, light signal is transmitted from the Gαq
PLC-mediated signaling to KCNQ/M channels: an example of receptor segregation
Neural KCNQ/M channels can be shut down by virtually any Gαq–PLC- or Gα11–PLC-coupled receptor 40, 41. Indeed, all of their putative subunits (KCNQ2–5) – and even the cardiac homolog KCNQ1 – appear to be equally susceptible to suppression by an appropriate Gαq- or Gα11-linked G-protein-coupled receptor [42]. Nevertheless, there seems to be some functional discrimination between different receptors, at least mechanistically.
Thus, KCNQ/M channels in sympathetic neurons are closed by ACh (the
Concluding remarks: new principles for PLC signaling
Because the PLCβ cascade is utilized by a large numbers of transmembrane receptors and is present in virtually all cells, a central question is how these cells generate receptor-specific signals. From the two examples discussed here, it appears that PLC signaling pathways are tightly coupled, forming architecturally distinct signaling complexes or microdomains. Two strategies also seem to emerge. In the first model, exemplified by the Drosophila phototransduction, the PLC signaling complex
Acknowledgements
Our work was supported by the Centre National de la Recherche Scientifique (CNRS) and by grants from the UK Medical Research Council and the Wellcome Trust.
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