Yamashita Kensuke, Shimane Kazuya, Muramoto Tetsuya
Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Development. 2025 Jan 1;152(1). doi: 10.1242/dev.204403. Epub 2025 Jan 14.
Oscillatory dynamics and their modulation are crucial for cellular decision-making; however, analysing these dynamics remains challenging. Here, we present a tool that combines the light-activated adenylate cyclase mPAC with the cAMP biosensor Pink Flamindo, enabling precise manipulation and real-time monitoring of cAMP oscillation frequencies in Dictyostelium. High-frequency modulation of cAMP oscillations induced cell aggregation and multicellular formation, even at low cell densities, such as a few dozen cells. At the population level, chemotactic aggregation is driven by modulated frequency signals. Additionally, modulation of cAMP frequency significantly reduced the amplitude of the shuttling behaviour of the transcription factor GtaC, demonstrating low-pass filter characteristics capable of converting subtle oscillation changes, such as from 6 min to 4 min, into gene expression. These findings enhance our understanding of frequency-selective cellular decoding and its role in cellular signalling and development.
振荡动力学及其调节对于细胞决策至关重要；然而，分析这些动力学仍然具有挑战性。在这里，我们展示了一种工具，它将光激活腺苷酸环化酶mPAC与cAMP生物传感器Pink Flamindo相结合，能够精确操纵并实时监测盘基网柄菌中cAMP振荡频率。即使在低细胞密度（如几十细胞）下，cAMP振荡的高频调节也能诱导细胞聚集和多细胞形成。在群体水平上，趋化性聚集由调节频率信号驱动。此外，cAMP频率的调节显著降低了转录因子GtaC穿梭行为的幅度，证明其具有低通滤波器特性，能够将细微的振荡变化（如从6分钟变为4分钟）转化为基因表达。这些发现增进了我们对频率选择性细胞解码及其在细胞信号传导和发育中的作用的理解。
