Cell Mol Biol (Noisy-le-grand). 2006 Dec 31;52(8):1-2.

Membrane transporters and signal transduction.

EDITORIAL The Na/K-ATPase was originally discovered by J.S. Skou in 1957 as an ion pump that hydrolyzes ATP to maintain the trans-membrane Na+ gradient. Although it was recognized a long time ago that the Na/K-ATPase is capable of interacting with many cellular proteins, recent investigations from many laboratories around the globe have made the connection between these protein interactions and the assembly of various Na/K-ATPase signaling complexes (signalosomes). Interestingly, other membrane transporters and channels are also actively engaged in various signaling events via their interactions with protein kinases, phosphatases and other cellular proteins. The assembly of an ion transporter-specific signalosome not only allows for a concerted regulation of the ion transporting networks, but also makes it possible for the transporter to regulate the function of the signaling network in a cell. In order to promote the recent appreciation of these membrane proteins in the transmission and integration of extracellular signals, a workshop entitled Molecular mechanisms of pump-channel-, and transporter-mediated signal transduction was organized within the Fourth World Congress on Cellular and Molecular Biology that was held in Poitiers, France from October 7-12, 2005. A total of twenty-six scientists from the fields of signal transduction, ion pumps, anion and cation channels, and transporters discussed the following three topics: 1. Protein interactions and the formation of a transporter-related signalosome; 2. Regulation of cellular functions by the signaling pumps, channels and transporters; and 3.Targeting the signaling pump, channel and transporters for new drug development. This thematic issue of Cellular Molecular Biology collected seventeen articles from these discussions. The first group of manuscripts explores the importance of the activation of the newly appreciated receptor function of Na/K-ATPase by endogenous cardiotonic steroids in the development of cardiovascular diseases. While Kennedy et al. summarized the present state of our understanding of the relationship between Na/K-ATPase-mediated signal transduction and uremic cardiomyopathy, Ferrandi et al. provided an in-depth discussion on ouabain-activated signaling in caveolae and its relationship to the development of hypertension. In addition, both manuscripts have presented evidence that the Na/K-ATPase receptor function can be targeted for the development of new therapeutics. In the manuscript by Averina et al., the potential role of cardiotonic steroids in the pathogenesis of preeclampsia was evaluated. Finally, Zvartau et al. provided evidence to suggest that marinobufagenin may be involved in obstructive sleep apnea-related hypertension. The second group of manuscripts delves into the molecular mechanisms of Na/K-ATPase-mediated signal transduction. Liu and Askari discuss the likely causes of the amplification of digitalis signal via the Na/K-ATPase. While Contreras et al. summarize their findings on Na/K-ATPase and cell attachment, Barwe et al. present evidence that protein kinase C is involved in Na/K-ATPase beta-subunit-mediated lamellipodia formation and suppression of cell motility in carcinoma cells. In skeletal muscle cells, Kotova et al. demonstrate that ouabain stimulates metabolic and signaling events. The contributions of Na/K-ATPase to signal transduction and cell growth in endothelial cells are reported by Scheiner-Bobis and Trevisis laboratories. The role of cardiotonic steroids in control of intracellular vesicle trafficking is discussed by Rosen et al. This is followed by an article from Orlovs laboratory showing that altered endo- and exocytoses evoked by cardiotonic steroids contribute to the rapid decline of MTT reduction in ouabain-treated cells. Finally, the potential interaction between hypokalemia and cardiotonic steroids in provoking signal transduction is assessed by Kennedy et al. The third group of manuscripts reveals the potential coupling between the Na/K-ATPase and other membrane transporters. Kawakami and Ikeda present experimental evidence showing that the alpha 2 isoform of Na/K-ATPase is important for the regulation of neural activities via direct coupling to KCC2. On the other hand, Liu proposes that there is an indirect coupling between the basolateral pumping and apical leaking in polarized renal epithelial cells. This coupling is likely mediated by ouabain-induced endocytosis of the Na/K-ATPase, and may play an important role in renal adaptation to volume overload and high salt intake. Finally, Khan et al. demonstrate that the NHE1 Na+/H+ exchanger regulates cell survival by activating and targeting ezrin to specific plasma membrane domains. In addition, Giamarchi et al. review the function of polycystin-2 as a cation channel and its interaction with other regulatory proteins. I would like to thank all of the contributors, especially the graduate students and postdoctoral fellows, for their endeavors. I would also like to thank the Committee of the Fourth World Congress on Cellular and Molecular Biology for providing us the opportunity for this workshop and Cellular and Molecular Biology for this thematic issue. Special appreciation also goes to Dr. Jean-Michel Maixent and his staff for the highest level of quality in composition and editing.

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