## 2 In This Special Issue  
[PERSON] et al. review recent efforts to engineer genetically-encoded fluorescence indicators to monitor the membrane voltage and the concentrations of Ca\({}^{2+}\) and K\({}^{+}\), as well as key neurotransmitters,changes in which accompany neuronal activity. This work serves as an excellent guide for selection of the most appropriate optogenetic reporters for a particular experiment. Optogenetic actuators are even more diverse than sensors, in both their nature and intended uses. In some cases, such as microbial rhodopsins, the functions of the photosensor and effector are executed by the same protein domain, whereas in other proteins a photosensory domain is followed by distinct effector domains. Examples of photosensory domains found in native multidomain proteins are small flavoprotein modules known as Light, Oxygen, or Voltage sensing (LOV) and Blue-Light-Utilizing Flavin-binding (BLUF) domains that respond to UV-A/blue light (320-500 nm) [6; 7]. Both these domains are widely used in optogenetic studies. In plant phototropins that contain LOV domains, photoexcitation of the chromophore flavin mononucleotide (FMN) leads to unfolding of the C-terminal J\(\alpha\) helix, to which various peptides of interest, such as nuclear localization and export signals, can be attached. [PERSON] and [PERSON] use a LOV domain-based light-inducible nuclear export system (LEXY) to manipulate cellular levels of the transcription factor p53 with blue light. In certain human cancers, excessive inactivation of p53 results from overexpression of its negative regulator, murine double minute 2 (Mdm2). The 12-amino-acid peptide, p53-Mdm2/MdmX inhibitor (PMI), binds to Mdm2 and suppresses its function. The authors show that in the dark, the PMI-LEXY fusion remains in the nucleus and prevents Mdm2 from degrading p53. Illumination caused export of the PMI-LEXY fusion to the cytosol, which released Mdm2. According to the authors, this optogenetic tool can be used to study the effects of local p53 activation within a tissue or organ. BLUF domains are mostly found in prokaryotes and usually bind flavin adenine dinucleotide (FAD) as a chromophore. They exhibit different photochemical reactions, as compared to LOV domains. [PERSON] et al. have analyzed 34 native BLUF domains from publicly accessible sequence databases. They have found functional association of these domains with several previously unknown effector domains, such as guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases (RhoGEF), phosphatidylinositol-ethanolamine binding protein (PBP), anyrin and leucine-rich repeats. This remarkable modular diversity of BLUF domain-containing proteins expands the repertoire of potential chimeric assemblies that can be created by a combination of BLUF domains with appropriate cellular effectors. Microbial rhodopsins, being electrogenic, are used to control the membrane voltage with light [8]. Channelrhodopsins mediate passive transport of ions along the electrochemical gradient and are therefore intrinsically more potent than rhodopsin ion pumps that translocate across the membrane only one ion per captured photon. Both cation- and anion-selective channelrhodopsins are known, abbreviated as CCRs and ACRs, respectively [9]. CCRs appear to emerge by convergent evolution by at least two independent routes. One CCR family was found in green (chlorophyte) flagellate algae, in which they act as photoreceptors for phototaxis [10]. Another CCR family that shows closer primary sequence homology to haloarchaeal rhodopsin pumps than to other known CCRs, was found in phylogenetically distant cryptophyte algae [11]. [PERSON] et al. characterize channel properties of CCR4 from the cryptophyte alga _Guillardia theta_ (GtCCR4).