A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons.
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.
Arteaga
Maria F
MF
Department of Cellular and Molecular Physiology, Yale University, 333 Cedar Street, New Haven, CT 06520, USA.
Coric
Tatjana
T
Straub
Christoph
C
Canessa
Cecilia M
CM
D062565:Acid Sensing Ion Channels; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D062565:Acid Sensing Ion Channels; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D017346:Protein Serine-Threonine Kinases; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases; C568267:ASIC1 protein, mouse