@article{WeschMirandaAfonsoOramasetal.2010,
  author    = {Diana Wesch and Pablo Miranda and Domingo Afonso-Oramas and Mike Althaus and Javier Castro-Hernandez and Jaime Dominguez and Rory E. Morty and Wolfgang Clauss and Tomas Gonzalez-Hernandez and Diego Alvarez de la Rosa and Teresa Giraldez},
  title     = {The neuronal-specific SGK1.1 kinase regulates δ-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling},
  series   = {American Journal of Physiology: Cell physiology},
  volume    = {299},
  number    = {4},
  publisher = {American Physiological Society},
  issn      = {0363-6143},
  doi       = {10.1152/ajpcell.00184.2010},
  year      = {2010},
  abstract  = {Wesch D, Miranda P, Afonso-Oramas D, Althaus M, Castro-Hernandez J, Dominguez J, Morty RE, Clauss W, Gonzalez-Hernandez T, Alvarez de la Rosa D, Giraldez T. The neuronalspecific SGK1.1 kinase regulates delta-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling. Am J Physiol Cell Physiol 299: C779-C790, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00184.2010.-The delta-subunit of the epithelial Na+ channel (ENaC) is expressed in neurons of the human and monkey central nervous system and forms voltage-independent, amiloride-sensitive Na+ channels when expressed in heterologous systems. It has been proposed that delta-ENaC could affect neuronal excitability and participate in the transduction of ischemic signals during hypoxia or inflammation. The regulation of delta-ENaC activity is poorly understood. ENaC channels in kidney epithelial cells are regulated by the serum-and glucocorticoid-induced kinase 1 (SGK1). Recently, a new isoform of this kinase (SGK1.1) has been described in the central nervous system. Here we show that delta-ENaC isoforms and SGK1.1 are coexpressed in pyramidal neurons of the human and monkey (Macaca fascicularis) cerebral cortex. Coexpression of delta beta gamma-ENaC and SGK1.1 in Xenopus oocytes increases amiloride-sensitive current and channel plasma membrane abundance. The kinase also exerts its effect when delta-subunits are expressed alone, indicating that the process is not dependent on accessory subunits or the presence of PY motifs in the channel. Furthermore, SGK1.1 action depends on its enzymatic activity and binding to phosphatidylinositol(4,5)-bisphosphate. Physiological or pharmacological activation of phospholipase C abrogates SGK1.1 interaction with the plasma membrane and modulation of delta-ENaC. Our data support a physiological role for SGK1.1 in the regulation of delta-ENaC through a pathway that differs from the classical one and suggest that the kinase could serve as an integrator of different signaling pathways converging on the channel.},
  language  = {en}
}