@article{TianYangGao2020,
  author    = {Tian, Yuehui and Yang, Shang and Gao, Shiqiang},
  title     = {Advances, perspectives and potential engineering strategies of light-gated phosphodiesterases for optogenetic applications},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21207544},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236203},
  year      = {2020},
  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.},
  language  = {en}
}
@article{MaiellaroLohseKitteetal.2016,
  author    = {Maiellaro, Isabella and Lohse, Martin J. and Kitte, Robert J. and Calebiro, Davide},
  title     = {cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons},
  series = {Cell Reports},
  volume    = {17},
  journal   = {Cell Reports},
  number    = {5},
  doi       = {10.1016/j.celrep.2016.09.090},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162324},
  pages     = {1238-1246},
  year      = {2016},
  abstract  = {The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons.},
  language  = {en}
}
@article{BeckYuStrzelczykPaulsetal.2018,
  author    = {Beck, Sebastian and Yu-Strzelczyk, Jing and Pauls, Dennis and Constantin, Oana M. and Gee, Christine E. and Ehmann, Nadine and Kittel, Robert J. and Nagel, Georg and Gao, Shiqiang},
  title     = {Synthetic light-activated ion channels for optogenetic activation and inhibition},
  series = {Frontiers in Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Neuroscience},
  number    = {643},
  doi       = {10.3389/fnins.2018.00643},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177520},
  year      = {2018},
  abstract  = {Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\)) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca\(^{2+}\) and K\(^{+}\) in cell physiology, light-activated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca\(^{2+}\) or for K\(^{+}\), respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca\(^{2+}\)-permeant channel, and to body extension when expressing the light-sensitive K\(^{+}\) channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons.},
  language  = {en}
}