title: Clozapine and lithium require Caenorhabditis elegans β-arrestin and serum- and glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization.
abstract: Numerous studies have implicated low levels of signaling in the Akt network with psychotic illnesses, and a growing body of literature has shown that all classes of antipsychotic drugs increase Akt signaling. The most clinically effective antipsychotic drug is clozapine. With Caenorhabditis elegans as a model system, this study demonstrates that clozapine is unique among antipsychotic drugs because it requires β-arrestin and serum and glucocorticoid-inducible kinase (SGK) in addition to Akt to suppress the nuclear localization of DAF-16 (Forkhead box O [FOXO]). Lithium, a mood stabilizer often used to treat psychosis, also requires β-arrestin and SGK to suppress the nuclear localization of DAF-16.
authors: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana 71130-3932, USA.
authors: Kathrine R
authors: KR
authors: Weeks
authors: Donard S
authors: DS
authors: Dwyer
authors: Eric J
authors: EJ
authors: Aamodt
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018692:Antimanic Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019390:Arrestins / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000502:physiology*; D018020:Lithium Compounds / Q000494:pharmacology*; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D000071557:beta-Arrestins; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D019390:Arrestins; D029742:Caenorhabditis elegans Proteins; D003024:Clozapine; D051858:Forkhead Transcription Factors; D017874:Immediate-Early Proteins; D018020:Lithium Compounds; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000071557:beta-Arrestins; D000099184:Serum-Glucocorticoid Regulated Kinases; C108831:daf-16 protein, C elegans