Synthetic retinals: convenient probes of rhodopsin and visual transduction process.
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The ERC is a conformation-dependent charge motion similar to the gating currents of ionic channels. Both the waveforms and bandwidth of ERCs and ionic channel gating currents are similar, providing support to the initial suggestion that the ERP was a kind of gating current. In ionic channels the electrostatic field promotes motion of alpha-helical elements that stimulate large-scale molecular events that promote opening of the ionic pore. In ionic channels gating currents of expressed channel mutants has contributed significantly to understanding the mechanism of activation. Given the known role of electrical processes to rhodopsin activation, the ERC approach applied to mutant and wild-type visual pigments is likely to lead to a fuller understanding of the mechanism of conformational activation. This method is currently well suited to investigate the later phases of rhodopsin activation that are thought to be electrostatic in nature. We anticipate that ERC studies will make significant contributions to understanding how the breakdown of the electrostatic interaction between the PSB and its counterion is initiated and propagated to induce the proton uptake on the cytoplasmic surface of the pigment and the shaping of the transducin docking domain. We encourage collaboration to apply the ERC methodology to interesting mutant pigments and retinal analogs. We expect that the ERC methodology can soon be applied to understand rapid charge displacements associated with photochemistry (i.e., R1), the effects of transduction proteins on R2, and the measurement of electrical processes during cone visual pigment activation.
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Rodents blind from outer retinal (rod and cone) degeneration still retain several light-dependent phenomena, including entrainment of the circadian clock and pupillary light responsiveness. This paradox is explained by the presence of intrinsically photosensitive retinal ganglion cells in the inner retina. These cells have unique properties, including a novel action spectrum, resistance to bleaching and adaptation under continuous light, and resistance to vitamin A depletion. Two candidate classes of photopigment have been proposed: melanopsin and cryptochromes. Physiologic analysis of circadian entrainment and pupillary light responsiveness in mice lacking these proteins leads to three conclusions: (1) outer and inner retinal photoreceptors provide partially redundant information to the inner retina, (2) melanopsin is required for inner retinal phototransduction in the absence of rod and cone signaling, and (3) cryptochromes contribute to the amplitude of inner retinal phototransduction but are not strictly required.
Paralogy (common ancestry through gene duplication rather than speciation) is widely recognized as an important problem for molecular systematists. This chapter introduces the concepts of paralogy and orthology and explains why paralogy can complicate both systematic work and other studies of molecular evolution. The definition of paralogy is explicitly phylogenetic, and phylogenetic methods are crucial in elucidating the pattern of paralogy. In particular, knowledge of the species phylogeny is key. I introduce the theory behind methods for detecting paralogy and briefly discuss two particular software implementations of phylogenetic methods to detect paralogy from molecular data. I also introduce a statistical method for detecting paralogy and some future directions for work on paralogy detection.
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