The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction

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RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293 cells and human iPSC-derived neurons, and delineate RBM12 as a novel repressor of the G...

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Autores principales: Semesta, Khairunnisa M., Garces, Angelica, Tsvetanova, Nikoleta G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502367/
https://www.ncbi.nlm.nih.gov/pubmed/37543364
http://dx.doi.org/10.1016/j.jbc.2023.105133
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author Semesta, Khairunnisa M.
Garces, Angelica
Tsvetanova, Nikoleta G.
author_facet Semesta, Khairunnisa M.
Garces, Angelica
Tsvetanova, Nikoleta G.
author_sort Semesta, Khairunnisa M.
collection PubMed
description RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293 cells and human iPSC-derived neurons, and delineate RBM12 as a novel repressor of the G protein–coupled receptor/cAMP/PKA (GPCR/cAMP/PKA) signaling axis. We establish that loss of RBM12 leads to hyperactive cAMP production and increased PKA activity as well as altered neuronal transcriptional responses to GPCR stimulation. Notably, the cAMP and transcriptional signaling steps are subject to discrete RBM12-dependent regulation. We further demonstrate that the two RBM12
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spelling pubmed-105023672023-09-16 The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction Semesta, Khairunnisa M. Garces, Angelica Tsvetanova, Nikoleta G. J Biol Chem Research Article RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293 cells and human iPSC-derived neurons, and delineate RBM12 as a novel repressor of the G protein–coupled receptor/cAMP/PKA (GPCR/cAMP/PKA) signaling axis. We establish that loss of RBM12 leads to hyperactive cAMP production and increased PKA activity as well as altered neuronal transcriptional responses to GPCR stimulation. Notably, the cAMP and transcriptional signaling steps are subject to discrete RBM12-dependent regulation. We further demonstrate that the two RBM12 American Society for Biochemistry and Molecular Biology 2023-08-04 /pmc/articles/PMC10502367/ /pubmed/37543364 http://dx.doi.org/10.1016/j.jbc.2023.105133 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Semesta, Khairunnisa M.
Garces, Angelica
Tsvetanova, Nikoleta G.
The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title_full The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title_fullStr The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title_full_unstemmed The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title_short The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction
title_sort psychosis risk factor rbm12 encodes a novel repressor of gpcr/camp signal transduction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502367/
https://www.ncbi.nlm.nih.gov/pubmed/37543364
http://dx.doi.org/10.1016/j.jbc.2023.105133
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