This might hint at a more general function of this redox protein, independent of a circadian clock. As LdpA is suggested to transfer redox signals from the photosynthetic electron transport chain to the circadian oscillator in S. elongatus ( Ivleva et al., Epacadostat chemical structure 2005), LdpA could be a general component of the photosynthetic machinery in Cyanobacteria. Because UCYN-A lacks photosystem II ( Bothe et
al., 2010, Thompson et al., 2012, Tripp et al., 2010 and Zehr et al., 2008), LdpA would be dispensable and explains the absence of an LdpA homolog. PexA as another component of the input machinery is present only in a limited number of the marine Cyanobacteria analyzed here and could constitute a transcription factor, which might target also genes that are not related to the circadian clock. The existence of three well-conserved pex genes in the Acaryochloris genome supports this idea. Regarding the output components of the clockwork, variability between the cyanobacterial strains seems to be not as evident as for the central oscillator and the input components. All species listed in Table 1 (except for Gloeobacter) hold, besides KaiC, a putative SasA and a RpaA protein that are similar in length to the respective S. elongatus proteins (400 aa and 350 aa, respectively). Thus, the KaiC-SasA-RpaA signaling cascade described earlier appears to play a key role in gene expression regulation in Cyanobacteria. Intriguingly, even STAT inhibitor Gloeobacter
holds a putative RpaA protein. This suggests that RpaA can be activated via other non-circadian signaling pathways anti-PD-1 antibody as it has already been suggested for S. elongatus ( Taniguchi et al., 2010). As described above, besides the SasA-dependent pathway, two other pathways have been identified that convert temporal information
into gene expression patterns. First, the LabA-dependent negative pathway exists, which appears to function by repressing the RpaA activity (Taniguchi et al., 2007 and Taniguchi et al., 2010). The mechanism of action has not yet been clarified. Second, the CikA-dependent negative pathway was uncovered in which CikA acts as a phosphatase that dephosphorylates RpaA (Gutu and O’Shea, 2013). Therefore, the two histidine kinases CikA with its dual role in input and output and SasA with its key output role work antagonistically to time the activation of circadian gene expression (Gutu and O’Shea, 2013). The combination of three different output pathways by SasA, CikA and LabA, all functioning through RpaA as a downstream element, likely secures the robustness of the circadian kaiBC expression ( Taniguchi et al., 2010). It might as well confer the opportunity for some fine tuning. Seven of the species listed in Table 1 contain both LabA and CikA and are hence possibly able to use the advantage of robust regulation by two independent negative feedback mechanisms. However, three marine organisms included in Table 1 do not possess a LabA protein and three lack a CikA homolog.