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SRF in Neurochemistry: Overview of Recent Advances in Research on the Nervous System

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Abstract

Serum response factor (SRF) is a representative transcription factor that plays crucial roles in various biological phenomena by regulating immediate early genes (IEGs) and genes related to cell morphology and motility, among others. Over the years, the signal transduction pathways activating SRF have been clarified and SRF-target genes have been identified. In this overview, we initially briefly summarize the basic biology of SRF and its cofactors, ternary complex factor (TCF) and megakaryoblastic leukemia (MKL)/myocardin-related transcription factor (MRTF). Progress in the generation of nervous system-specific knockout (KO) or genetically modified mice as well as genetic analyses over the last few decades has not only identified novel SRF-target genes but also highlighted the neurochemical importance of SRF and its cofactors. Therefore, here we next present the phenotypes of mice with nervous system-specific KO of SRF or its cofactors by depicting recent findings associated with brain development, plasticity, epilepsy, stress response, and drug addiction, all of which result from function or dysfunction of the SRF axis. Last, we develop a hypothesis regarding the possible involvement of SRF and its cofactors in human neurological disorders including neurodegenerative, psychiatric, and neurodevelopmental diseases. This overview should deepen our understanding, highlight promising future directions for developing novel therapeutic strategies, and lead to illumination of the mechanisms underlying higher brain functions based on neuronal structure and function.

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Abbreviations

AAV:

Adeno-associated virus

AD:

Alzheimer’s disease

ALS:

Amyotrophic sclerosis

Arc:

Activity-regulated cytoskeleton-associated protein

ASD:

Autism spectrum disorder

BDNF:

Brain-derived neurotrophic factor

BSAC:

Basic, SAP, and coiled-coil domain

CaMK:

Calcium/calmodulin-dependent protein kinase

CArG:

CC(AT)6GG

CBP:

CREB-binding protein

Cdk:

Cyclin-dependent kinase

CREB:

cAMP response element-binding protein

CRISPR/Cas:

Clustered regularly interspaced short palindromic repeat/CRISPR-associated

CTGF:

Connective tissue growth factor

DAT:

Dopamine active transporter

D1:

Dopamine D1 receptor

DG:

Dentate gyrus

DRG:

Dorsal root ganglion

EE:

Enriched environment

egr:

Early growth response

Elk:

Ets-like transcription factor

ERP:

Ets-related protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GFAP:

Glial fibrillary acidic protein

HSV:

Herpes simplex virus

IEG:

Immediate early gene

LTD:

Long-term depression

LTP:

Long-term potentiation

LPA:

Lysophosphatidic acid

MADS:

Minichromosome maintenance 1 protein, agamous, deficiens, and SRF

MKL:

Megakaryoblastic leukemia

MRTF:

Myocardin-related transcription factor

MEF2:

Myocyte enhancer factor 2

NAc:

Nucleus accumbens

Net:

New Ets transcription factor

NEX:

Neuronal helix-loop-helix

NGF:

Nerve growth factor

NPC:

Neural precursor cell

PD:

Parkinson’s disease

RyR:

Ryanodine receptor

SAP:

SRF accessory protein

SARE:

Synaptic activity-responsive element

SNP:

Single-nucleotide polymorphism

SRF:

Serum response factor

SUMO:

Small ubiquitin-like modifier

TCF:

Ternary complex factor

TF:

Transcription factor

TGF-β:

Transforming growth factor-β

VSMC:

Vascular smooth muscle cell

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Acknowledgements

We thank all members of the Laboratory of Molecular Neurobiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, for their assistance with this work. We also thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by JSPS KAKENHI grant numbers JP26460064 (AT) and JP18K06625 (AT), and grants from the Tamura Science and Technology Foundation (AT), the Toyama First Bank Foundation (AT), and the Smoking Research Foundation (AT).

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  1. Laboratory of Molecular Neurobiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Akiko Tabuchi & Daisuke Ihara

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  1. Akiko Tabuchi
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AT wrote the manuscript. DI assisted in arranging the reference section and making the tables and figures. All authors edited and revised the manuscript and approved its final version for publication.

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Tabuchi, A., Ihara, D. SRF in Neurochemistry: Overview of Recent Advances in Research on the Nervous System. Neurochem Res 47, 2545–2557 (2022). https://doi.org/10.1007/s11064-022-03632-x

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