GABAA receptor subunit beta1 is involved in the formation of protease-resistant prion protein in prion-infected neuroblastoma cells.
Gamma-aminobutyric acid type A (GABAA) receptor beta1 (gabrb1), a subunit of GABAA receptors involved in inhibitory effects on neurotransmission, was found to associate with the formation of protease-resistant prion protein in prion-infected neuroblastoma cells. Silencing of gabrb1 gene expression significantly decreased the abnormal prion protein level but paradoxically increased the normal prion protein level. Treatment with a gabrb1-specific inhibitor, salicylidene salicylhydrazide, dose-dependently decreased the abnormal prion protein level, but silencing of other GABAA receptor subunits' gene expression and treatments with the receptor antagonists and agonists did not. Therefore, gabrb1 involvement in abnormal prion protein formation is independent of GABAA receptors.
Kimura
Tomohiro
T
Department of Prion Research, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Ishikawa
Kensuke
K
Sakasegawa
Yuji
Y
Teruya
Kenta
K
Sata
Tetsutaro
T
Schätzl
Hermann
H
Doh-ura
Katsumi
K
D000818:Animals; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004351:Drug Resistance / Q000235:genetics; D058787:GABA-A Receptor Antagonists; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009447:Neuroblastoma / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism / Q000494:pharmacology; D017096:Prion Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000378:metabolism* / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; C546266:Gabrb1 protein, mouse; D050505:Mutant Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D010447:Peptide Hydrolases