Present address: Laboratory of Embryonic Stem Cell Biology, STRIP Monash University, Clayton, Vic. 3800, Australia.
S1P inhibits gap junctions in astrocytes: involvement of Gi and Rho GTPase/ROCK
Article first published online: 21 MAR 2006
European Journal of Neuroscience
Volume 23, Issue 6, pages 1453–1464, March 2006
How to Cite
Rouach, N., Pébay, A., Même, W., Cordier, J., Ezan, P., Etienne, E., Giaume, C. and Tencé, M. (2006), S1P inhibits gap junctions in astrocytes: involvement of Gi and Rho GTPase/ROCK. European Journal of Neuroscience, 23: 1453–1464. doi: 10.1111/j.1460-9568.2006.04671.x
Present address: Laboratoire de Neurobiologie, UPRES EA 2633, Université d'Orléans, BP 6759, 45067 Orléans cedex 2, France.
- Issue published online: 21 MAR 2006
- Article first published online: 21 MAR 2006
- Received 1 September 2005, revised 12 December 2005, accepted 1 January 2006
- actin cytoskeleton;
- Rho GTPases;
Sphingosine-1-phosphate (S1P) is a potent and pleiotropic bioactive lysophospholipid mostly released by activated platelets that acts on its target cells through its own G protein-coupled receptors. We have previously reported that mouse striatal astrocytes expressed mRNAs for S1P1 and S1P3 receptors and proliferate in response to S1P. Here, we investigated the effect of S1P on gap junctions. We show that a short-term exposure of astrocytes to S1P causes a robust inhibition of gap junctional communication, as demonstrated by dye coupling experiments and double voltage-clamp recordings of junctional currents. The inhibitory effect of S1P on dye coupling involves the activation of both Gi and Rho GTPases. Rho-associated kinase (ROCK) also plays a critical role. The capacity of S1P to activate a Rho/ROCK axis in astrocytes is demonstrated by the typical remodeling of actin cytoskeleton. Connexin43, the protein forming gap junction channels, is a target of the Gi- and Rho/ROCK-mediated signaling cascades. Indeed, as shown by Western blots and confocal immunofluorescence, its nonphosphorylated form increases following S1P treatment and this change does not occur when both cascades are disrupted. This novel effect of S1P may have an important physiopathological significance when considering the proposed roles for astrocyte gap junctions on neuronal survival.