激光调控细胞钙信号的技术与机制  

Technique and Mechanism of Modulating Cellular Ca^(2+) Signaling Using Laser

作　　者：田晓莹 贺号 Tian Xiaoying;He Hao(School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai 200030,China)

机构地区：[1]上海交通大学生物医学工程学院,上海200030

出　　处：《中国激光》2023年第3期193-203,共11页Chinese Journal of Lasers

基　　金：国家自然科学基金(62022056,61975118)。

摘　　要：钙离子是细胞内重要的第二信使,调节基因转录、能量合成及细胞增殖和凋亡等功能。细胞膜与细胞器上钙相关蛋白协同作用,形成复杂而有序的钙信号网络。在亚细胞结构上特异性激活与抑制某个钙相关蛋白而不影响其他蛋白及其他细胞器能够极大促进亚细胞结构钙信号调节机制及相关功能研究。然而,由于药物在细胞内的自由扩散及蛋白在细胞内的广泛表达,药物的分子特异性及空间特异性有限,因此基于激光的钙信号调节方法得到发展。主要讨论了光解锁笼、光遗传以及全光调控三种基于激光的高空间分辨率的细胞内钙信号调控技术的优点及局限性。理论上,它们对细胞的刺激可以局限在亚微米区域。特别地,分析阐述了基于多光子激发的低功率近红外飞秒激光调控细胞内钙信号的新型技术与机制。Significance Ca^(2+),an intracellular second messenger,is crucial for cell proliferation,differentiation,metabolism,and programmed cell death by participating in gene transcription,protein modification,adenosine triphosphate (ATP) generation,and the initiation of numerous signaling pathway cascades.Intracellular Ca^(2+) is first arrested by the plasma membrane,the first barrier that maintains an approximately 20000-fold Ca2+concentration gradient from the extracellular environment to the cytosol,by controlling Ca^(2+) influx and efflux through a series of Ca2+channels.Cytoplasmic Ca2+concentration is maintained at approximately 100 nmol/L in most non-excitable cells.Excess cytosolic Ca2+can be chelated by Ca2+-binding proteins,compartmentalized into intracellular Ca2+stores,or extruded into the extracellular environment.Organelles typically play the role of subcellular Ca2+stores (or temporary Ca2+buffers) and further synergize with each other to form a Ca2+network.As nodes on the network,they coordinate with the plasma membrane (PM) to regulate intracellular Ca2+signaling.The endoplasmic reticulum (ER) is the primary Ca2+store,with a resting Ca2+concentration of approximately 200μmol/L,releasing free Ca2+into the cytoplasm.Mitochondria are temporary calcium buffers that transiently accommodate excess Ca2+in the cytosol.Lysosomes and Golgi are small,but important in Ca2+signaling.Among these subcellular structures,the nucleus appears to be a mist for cell calcium research.However,little is known about the existence of Ca2+stores in the nucleus,how nuclear Ca2+is regulated,or how Ca2+is transported through the nuclear membrane.There are lots of membrane contact sites (MCSs) between organelles,such as ER-mitochondria,ER-PM,and ER-nucleus contacts.Local Ca2+interactions at the MCSs also perform vital cellular functions.A ubiquitous broad group of Ca2+sensors,channels,pumps,exchangers,and binding proteins (receptors) in subcellular structures regulate intracellular Ca2+for dynamic hemostasis.Ca2+signaling modulation

关 键 词：生物光学 多光子激发 光解锁笼 光遗传 全光调控 飞秒激光 

分 类 号：Q631[生物学—生物物理学] R318.51[医药卫生—生物医学工程]