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The actin-binding protein CAP1 represses MRTF-SRF-dependent gene expression in mouse cerebral cortex
Sharof Khudayberdiev1,2, Kerstin Weiss1, Anika Heinze1
1Molecular Neurobiology Group, Institute of Physiological Chemistry, Philipps-University of Marburg, 35032 Marburg, Germany.
Science Signaling
|May 7, 2024
Summary
Cyclase-associated protein CAP1 represses brain transcription factor activity. CAP1 inactivation promotes nuclear translocation of MRTF, activating SRF-dependent signaling crucial for neuronal network formation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Serum response factor (SRF) is vital for brain development and function.
- Myocardin-related transcription factor (MRTF) is an SRF cofactor that senses actin monomers.
- Regulation of MRTF-SRF activity is critical for neuronal processes.
Purpose of the Study:
- To investigate the regulation of MRTF by its cofactor, cyclase-associated protein CAP1, in mouse cortical neurons.
- To elucidate the role of CAP1 in controlling MRTF-SRF transcriptional activity in vivo and in vitro.
- To identify downstream targets of MRTF-SRF signaling regulated by CAP1.
Main Methods:
- In vitro and in vivo experiments using mouse cortical neurons.
- Assessment of MRTF nuclear translocation and SRF activity.
- Actin monomer levels measurement.
- Transcriptomic and proteomic analyses in wild-type and Cap1 knockout mice.
- Bioinformatic analysis of gene targets.
Main Results:
- Cyclase-associated protein CAP1 represses MRTF-dependent SRF activity.
- CAP1 inactivation reduces cytoplasmic actin monomers, promoting nuclear MRTF translocation and SRF activation.
- This regulation is independent of cofilin1 and actin-depolymerizing factor.
- Transcriptomic and proteomic data confirm CAP1's role in repressing MRTF-SRF signaling in vivo.
- Bioinformatic analysis identified potential MRTF-SRF target genes.
Conclusions:
- CAP1 acts as a key repressor of MRTF-SRF signaling in the brain.
- CAP1's regulation of actin dynamics is crucial for neuronal function, including synaptic plasticity and network formation.
- These findings highlight CAP1 as a significant regulator of neuronal development and function through actin dynamics.
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