Abstract
The second messengers, cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), play important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light, and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. The spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities for spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase genes from protists established a new and direct biological connection between light and PDEs. Light-regulated PDEs are under development, and of demand to complete the toolkit for cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs, and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.
Highlights
Introduction to Cyclic Nucleotides and Signal Transduction. First messengers such as light, nitric oxide (NO), and hormones can regulate intracellular second messenger cyclic adenosine 3 -5 -monophosphate(cAMP) and cyclic guanosine 3 -5 -monophosphate levels, which further affect the vision signaling, muscle contraction, cardiovascular, memory, and many other functions [1,2,3,4]. cyclic adenosine -5 -monophosphate (cAMP) is produced by adenylyl cyclases (ACs), which are divided into six classes [5,6]
AC10 can be activated by bicarbonate and plays an important role in sperm motility and fertilization capacity [8,9]
It was expected that light-induced PDEs could be designed and applied in addition to light-gated nucleotide cyclases, to regulate cyclic guanosine -5 -monophosphate (cGMP) or cAMP levels and dissect the related physiological processes
Summary
First messengers such as light, nitric oxide (NO), and hormones can regulate intracellular second messenger cyclic adenosine 3 -5 -monophosphate(cAMP) and cyclic guanosine 3 -5 -monophosphate (cGMP) levels, which further affect the vision signaling, muscle contraction, cardiovascular, memory, and many other functions [1,2,3,4]. cAMP is produced by adenylyl cyclases (ACs), which are divided into six classes [5,6]. Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and participates in physiological processes such as vasodilatation [17,18,19]. Soluble guanylyl cyclase (sGC) is activated by nitric oxide (INnt.OJ.)Maonl.dSpci.a2r0t2ic0i,p21a,t7e5s44in physiological processes such as vasodilatation [17,18,19]. PKAs are tethered by different A-kinase anchoring proteins (AKAPs) to distinct cell compartments, where different subcellular signalosomes are organized [32,33,34]. To study the rapid processes that regulate cGMP or cAMP levels in subcellular compartments, spatiotemporally precise methods are needed. It was expected that light-induced PDEs could be designed and applied in addition to light-gated nucleotide cyclases, to regulate cGMP or cAMP levels and dissect the related physiological processes
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