Neuronal activity-dependent SRF target gene expression via nuclear translocation of the SRF coactivator MRTFB

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15989
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: University of Toyama
• Principal Investigator: Ihara Daisuke 富山大学, 学術研究部薬学・和漢系, 助教 (20804561)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 遺伝子発現 / シナプス / 転写因子 / SRF / MRTF / MKL

Outline of Final Research Achievements

Myocardin-related transcription factors (MRTFs), highly expressed in the brain, have actin-binding motifs and function as transcriptional cofactors of serum response factor (SRF). Recently, we reported that MRTFs are localized in postsynapses and involved in synaptic maturation. However, it remains unclear how MRTFs are involved in activity-dependent gene expression in neurons. Therefore, we hypothesized that MRTFs, which exist in postsynapses, act as a transducer of synapse-to-nucleus signaling and analyzed their functions in primary cultured rat cortical neurons. We found that synaptic activation-induced the nuclear translocation of MRTFB and the expression of some SRF target genes are inhibited by blockage of NMDA receptor/L-VDCC, calcineurin and Rho signaling pathway in neurons. Taken together, these findings suggest that MRTFB is a novel key molecule which contributes to the synapse-to-nuclear signaling for neuronal plasticity.

Free Research Field

分子神経生物学

Academic Significance and Societal Importance of the Research Achievements

近年、MRTFAは統合失調症、MRTFBは自閉症スペクトラム症および知的障害や軽度の形態異常の原因遺伝子候補となっている。本研究により、脳神経系における「MRTFを介した遺伝子発現機構」および「MRTFの分子種間におけるその違い」を明らかにすることで、精神疾患や発達障害の病態解明につなげる。さらに将来的には、MRTFをターゲットとした新たな分子標的創薬につなげ、患者および家族のメンタルヘルス向上に貢献できる。