A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons

Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4459-64. doi: 10.1073/pnas.0800958105. Epub 2008 Mar 11.

Abstract

Neurodegenerative diseases and noxious stimuli to the brain enhance transcription of serum- and glucocorticoid-induced kinase-1 (SGK1). Here, we report that the SGK1 gene encodes a brain-specific additional isoform, SGK1.1, which exhibits distinct regulation, properties, and functional effects. SGK1.1 decreases expression of the acid-sensing ion channel-1 (ASIC1); thereby, SGK1.1 may limit neuronal injury associated to activation of ASIC1 in ischemia. Given that neurons express at least two splice isoforms, SGK1 and SGK1.1, driven by distinct promoters, any changes in SGK1 transcript level must be examined to define the isoform induced by each stimulus or neurological disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cricetinae
  • Immediate-Early Proteins / chemistry
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Organ Specificity
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sodium Channels / metabolism*

Substances

  • ASIC1 protein, mouse
  • Acid Sensing Ion Channels
  • Immediate-Early Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Sodium Channels
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase