Smedler Erik, Uhlén Per
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Biochim Biophys Acta. 2014 Mar;1840(3):964-9. doi: 10.1016/j.bbagen.2013.11.015. Epub 2013 Nov 22.
Calcium (Ca(2+)) oscillations are ubiquitous signals present in all cells that provide efficient means to transmit intracellular biological information. Either spontaneously or upon receptor ligand binding, the otherwise stable cytosolic Ca(2+) concentration starts to oscillate. The resulting specific oscillatory pattern is interpreted by intracellular downstream effectors that subsequently activate different cellular processes. This signal transduction can occur through frequency modulation (FM) or amplitude modulation (AM), much similar to a radio signal. The decoding of the oscillatory signal is typically performed by enzymes with multiple Ca(2+) binding residues that diversely can regulate its total phosphorylation, thereby activating cellular program. To date, NFAT, NF-κB, CaMKII, MAPK and calpain have been reported to have frequency decoding properties.
The basic principles and recent discoveries reporting frequency decoding of FM Ca(2+) oscillations are reviewed here.
A limited number of cellular frequency decoding molecules of Ca(2+) oscillations have yet been reported. Interestingly, their responsiveness to Ca(2+) oscillatory frequencies shows little overlap, suggesting their specific roles in cells.
Frequency modulation of Ca(2+) oscillations provides an efficient means to differentiate biological responses in the cell, both in health and in disease. Thus, it is crucial to identify and characterize all cellular frequency decoding molecules to understand how cells control important cell programs.
钙（Ca(2+)）振荡是所有细胞中普遍存在的信号，它提供了传递细胞内生物信息的有效方式。无论是自发的还是在受体配体结合后，原本稳定的胞质Ca(2+)浓度开始振荡。产生的特定振荡模式由细胞内下游效应器解读，这些效应器随后激活不同的细胞过程。这种信号转导可以通过频率调制（FM）或幅度调制（AM）发生，这与无线电信号非常相似。振荡信号的解码通常由具有多个Ca(2+)结合残基的酶来执行，这些酶可以不同程度地调节其总磷酸化，从而激活细胞程序。迄今为止，已有报道称NFAT、NF-κB、CaMKII、MAPK和钙蛋白酶具有频率解码特性。
本文综述了报道FM Ca(2+)振荡频率解码的基本原理和最新发现。
目前报道的Ca(2+)振荡的细胞频率解码分子数量有限。有趣的是，它们对Ca(2+)振荡频率的反应几乎没有重叠，这表明它们在细胞中具有特定作用。
Ca(2+)振荡的频率调制为区分健康和疾病状态下细胞中的生物学反应提供了一种有效手段。因此，识别和表征所有细胞频率解码分子对于理解细胞如何控制重要的细胞程序至关重要。
