Laboratory of Dr. Jin Zhang, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine Baltimore, Maryland, USA.
Front Cell Neurosci. 2014 Dec 4;8:395. doi: 10.3389/fncel.2014.00395. eCollection 2014.
The second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in signal transduction. The development of genetically encodable fluorescent biosensors has provided researchers with useful tools to study these versatile second messengers and their downstream effectors with unparalleled spatial and temporal resolution in cultured cells and living animals. In this review, we introduce the general design of these fluorescent biosensors and describe several of them in more detail. Then we discuss a few examples of using cyclic nucleotide fluorescent biosensors to study regulation of neuronal function and finish with a discussion of advances in the field. Although there has been significant progress made in understanding how the specific signaling of cyclic nucleotide second messengers is achieved, the mechanistic details in complex cell types like neurons are only just beginning to surface. Current and future fluorescent protein reporters will be essential to elucidate the role of cyclic nucleotide signaling dynamics in the functions of individual neurons and their networks.
第二信使环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)将来自激素和神经递质的许多神经调质信号转导为特定的功能输出。它们的产生、降解和信号转导受到时空调节，以实现信号转导的高度特异性。遗传可编码的荧光生物传感器的发展为研究人员提供了有用的工具，可在培养细胞和活体动物中以无与伦比的时空分辨率研究这些多功能第二信使及其下游效应物。在这篇综述中，我们介绍了这些荧光生物传感器的一般设计，并更详细地描述了其中的几个。然后，我们讨论了使用环核苷酸荧光生物传感器研究神经元功能调节的几个实例，并以该领域的进展作为讨论的结束。尽管人们在理解如何实现特定的环核苷酸第二信使信号方面已经取得了重大进展，但在神经元等复杂细胞类型中，其机制细节才刚刚开始显现。当前和未来的荧光蛋白报告基因将是阐明环核苷酸信号转导动态在单个神经元及其网络功能中的作用的关键。
