The actin-binding protein CAP1 represses MRTF-SRF-dependent gene expression in mouse cerebral cortex.
Sci Signal
; 17(835): eadj0032, 2024 05 07.
Article
en En
| MEDLINE
| ID: mdl-38713765
ABSTRACT
Serum response factor (SRF) is an essential transcription factor for brain development and function. Here, we explored how an SRF cofactor, the actin monomer-sensing myocardin-related transcription factor MRTF, is regulated in mouse cortical neurons. We found that MRTF-dependent SRF activity in vitro and in vivo was repressed by cyclase-associated protein CAP1. Inactivation of the actin-binding protein CAP1 reduced the amount of actin monomers in the cytoplasm, which promoted nuclear MRTF translocation and MRTF-SRF activation. This function was independent of cofilin1 and actin-depolymerizing factor, and CAP1 loss of function in cortical neurons was not compensated by endogenous CAP2. Transcriptomic and proteomic analyses of cerebral cortex lysates from wild-type and Cap1 knockout mice supported the role of CAP1 in repressing MRTF-SRF-dependent signaling in vivo. Bioinformatic analysis identified likely MRTF-SRF target genes, which aligned with the transcriptomic and proteomic results. Together with our previous studies that implicated CAP1 in axonal growth cone function as well as the morphology and plasticity of excitatory synapses, our findings establish CAP1 as a crucial actin regulator in the brain relevant for formation of neuronal networks.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transactivadores
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Corteza Cerebral
/
Actinas
/
Factor de Respuesta Sérica
/
Proteínas de Microfilamentos
Límite:
Animals
Idioma:
En
Revista:
Sci Signal
Asunto de la revista:
CIENCIA
/
FISIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos