Summary: Light driven chloride ion pumps that are ubiquitously found in halophilic archaea (HALOBACTERIALES).

Top Publications

  1. Zhao S, Cunha C, Zhang F, Liu Q, Gloss B, Deisseroth K, et al. Improved expression of halorhodopsin for light-induced silencing of neuronal activity. Brain Cell Biol. 2008;36:141-54 pubmed publisher
    ..Thus, the improved version of NpHR should serve as an excellent tool for neuronal silencing in vitro and in vivo. ..
  2. Chizhov I, Engelhard M. Temperature and halide dependence of the photocycle of halorhodopsin from Natronobacterium pharaonis. Biophys J. 2001;81:1600-12 pubmed
    ..It is proposed that P(4) and P(5) represent the anion release and uptake steps. Based on the experimental data affinities of the halide binding sites are estimated...
  3. Seki A, Miyauchi S, Hayashi S, Kikukawa T, Kubo M, Demura M, et al. Heterologous expression of Pharaonis halorhodopsin in Xenopus laevis oocytes and electrophysiological characterization of its light-driven Cl- pump activity. Biophys J. 2007;92:2559-69 pubmed
    ..We have also analyzed the kinetics of voltage-dependent Cl- pump activity as well as that of the photocycle. Based on these data, a kinetic model for voltage-dependent Cl- transport via pHR is presented...
  4. Zhang F, Wang L, Brauner M, Liewald J, Kay K, Watzke N, et al. Multimodal fast optical interrogation of neural circuitry. Nature. 2007;446:633-9 pubmed
    ..NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits. ..
  5. Sharma A, Walsh D, Bapteste E, Rodriguez Valera F, Ford Doolittle W, Papke R. Evolution of rhodopsin ion pumps in haloarchaea. BMC Evol Biol. 2007;7:79 pubmed
    ..In this initial study, we assess the roles of LGT and gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using phylogenetics and comparative genomics approaches...
  6. Lanyi J, Duschl A, Hatfield G, May K, Oesterhelt D. The primary structure of a halorhodopsin from Natronobacterium pharaonis. Structural, functional and evolutionary implications for bacterial rhodopsins and halorhodopsins. J Biol Chem. 1990;265:1253-60 pubmed
    ..Comparison of the bacteriorhodopsin sequence with those of the two halorhodopsins, on the other hand, identifies features involved in their specific (proton and chloride ion) transport ..
  7. Zhang F, Prigge M, Beyrière F, Tsunoda S, Mattis J, Yizhar O, et al. Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat Neurosci. 2008;11:631-3 pubmed publisher
    ..These results demonstrate fast photostimulation with yellow light, thereby defining a functionally distinct third category of microbial rhodopsin proteins...
  8. Krook Magnuson E, Armstrong C, Oijala M, Soltesz I. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nat Commun. 2013;4:1376 pubmed publisher
    ..A clinical approach built on these principles may overcome many of the side-effects of currently available treatment options. ..
  9. Zhang Y, Ivanova E, Bi A, Pan Z. Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in retinas with photoreceptor degeneration. J Neurosci. 2009;29:9186-96 pubmed publisher
    ..Our results suggest that the expression of multiple microbial rhodopsins such as ChR2 and HaloR is a possible strategy to restore both ON and OFF light responses in the retina after the death of rod and cone photoreceptors. ..

More Information


  1. Royant A, Nollert P, Edman K, Neutze R, Landau E, Pebay Peyroula E, et al. X-ray structure of sensory rhodopsin II at 2.1-A resolution. Proc Natl Acad Sci U S A. 2001;98:10131-6 pubmed
    ..The high-resolution structure of pSRII provides a structural basis to elucidate the mechanisms of phototransduction and color tuning...
  2. Tsunematsu T, Kilduff T, Boyden E, Takahashi S, Tominaga M, Yamanaka A. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci. 2011;31:10529-39 pubmed publisher
    ..The results presented here advance our understanding of the role of orexin neurons in the regulation of sleep/wakefulness and may be relevant to the mechanisms that underlie symptom progression in narcolepsy. ..
  3. Kolbe M, Besir H, Essen L, Oesterhelt D. Structure of the light-driven chloride pump halorhodopsin at 1.8 A resolution. Science. 2000;288:1390-6 pubmed
    ..Ion dragging across the protonated Schiff base explains why chloride and proton translocation modes are mechanistically equivalent in archaeal rhodopsins...
  4. Madisen L, Mao T, Koch H, Zhuo J, Berenyi A, Fujisawa S, et al. A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat Neurosci. 2012;15:793-802 pubmed publisher
    ..When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy. ..
  5. Ihara K, Umemura T, Katagiri I, Kitajima Ihara T, Sugiyama Y, Kimura Y, et al. Evolution of the archaeal rhodopsins: evolution rate changes by gene duplication and functional differentiation. J Mol Biol. 1999;285:163-74 pubmed
    ..The changes in evolution rate by gene duplication and functional differentiation were demonstrated in the archaeal rhodopsin family using the gene duplication date and halobacterial speciation date as common time stamps. ..
  6. Scharf B, Engelhard M. Blue halorhodopsin from Natronobacterium pharaonis: wavelength regulation by anions. Biochemistry. 1994;33:6387-93 pubmed
    ..Pharaonis hR reconstituted with azide shows photochemical reactions similar to the photocycle of bacteriorhodopsin.(ABSTRACT TRUNCATED AT 250 WORDS)..
  7. Kokaia M. Light-activated channels in acute seizures. Epilepsia. 2011;52 Suppl 8:16-8 pubmed publisher
    ..Our data suggest that optogenetic approach may become a useful method for controlling epileptiform activity, and may open novel avenues to develop alternative treatment strategies for epilepsy. ..
  8. Yamashita Y, Kikukawa T, Tsukamoto T, Kamiya M, Aizawa T, Kawano K, et al. Expression of salinarum halorhodopsin in Escherichia coli cells: solubilization in the presence of retinal yields the natural state. Biochim Biophys Acta. 2011;1808:2905-12 pubmed publisher
    ..Upon solubilization, HsHR expressed in the E. coli membrane attains the proper folding and a trimeric assembly comparable to those in the native membranes. ..
  9. Schoonheim P, Arrenberg A, Del Bene F, Baier H. Optogenetic localization and genetic perturbation of saccade-generating neurons in zebrafish. J Neurosci. 2010;30:7111-20 pubmed publisher
  10. Gradinaru V, Mogri M, Thompson K, Henderson J, Deisseroth K. Optical deconstruction of parkinsonian neural circuitry. Science. 2009;324:354-9 pubmed publisher
  11. Arrenberg A, Del Bene F, Baier H. Optical control of zebrafish behavior with halorhodopsin. Proc Natl Acad Sci U S A. 2009;106:17968-73 pubmed publisher
    ..Together this "optogenetic toolkit" allows loss-of-function and gain-of-function analyses of neural circuitry at high spatial and temporal resolution in a behaving vertebrate. ..
  12. Kuhara A, Ohnishi N, Shimowada T, Mori I. Neural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans. Nat Commun. 2011;2:355 pubmed publisher
    ..Thus, dual neural regulation in opposite directions is directly coupled to behavioural inversion in the simple neural circuit. ..
  13. Kouyama T, Kanada S, Takeguchi Y, Narusawa A, Murakami M, Ihara K. Crystal structure of the light-driven chloride pump halorhodopsin from Natronomonas pharaonis. J Mol Biol. 2010;396:564-79 pubmed publisher
  14. Tye K, Prakash R, Kim S, Fenno L, Grosenick L, Zarabi H, et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature. 2011;471:358-62 pubmed publisher
  15. Klare J, Bordignon E, Engelhard M, Steinhoff H. Sensory rhodopsin II and bacteriorhodopsin: light activated helix F movement. Photochem Photobiol Sci. 2004;3:543-7 pubmed
    ..In the second part, the helix F movement observed for both sensory rhodopsin and bacteriorhodopsin is evaluated and discussed in order to establish a common mechanism after photoreceptor activation. ..
  16. Bergo V, Spudich E, Spudich J, Rothschild K. Conformational changes detected in a sensory rhodopsin II-transducer complex. J Biol Chem. 2003;278:36556-62 pubmed
    ..These findings are discussed in the context of a recently elucidated x-ray structure of the fusion complex...
  17. Gordeliy V, Labahn J, Moukhametzianov R, Efremov R, Granzin J, Schlesinger R, et al. Molecular basis of transmembrane signalling by sensory rhodopsin II-transducer complex. Nature. 2002;419:484-7 pubmed
    ..94 A resolution, which provides an atomic picture of the first signal transduction step. Our results provide evidence for a common mechanism for this process in phototaxis and chemotaxis...
  18. Sato M, Kanamori T, Kamo N, Demura M, Nitta K. Stopped-flow analysis on anion binding to blue-form halorhodopsin from Natronobacterium pharaonis: comparison with the anion-uptake process during the photocycle. Biochemistry. 2002;41:2452-8 pubmed
    ..These observations suggest that the O-intermediate is similar to phR(blue) and that Cl- uptake during the photocycle may be ruled by a passive process...
  19. Spudich J. Variations on a molecular switch: transport and sensory signalling by archaeal rhodopsins. Mol Microbiol. 1998;28:1051-8 pubmed
    ..A model for signalling is proposed in which the salt bridge-controlled half-channel is used to modulate interaction with the Htr proteins when the receptor signalling states are formed. ..
  20. Gradinaru V, Thompson K, Deisseroth K. eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol. 2008;36:129-39 pubmed publisher
    ..The new enhanced NpHR (eNpHR) allows safe, high-level expression in mammalian neurons, without toxicity and with augmented inhibitory function, in vitro and in vivo. ..
  21. Zhang W, Brooun A, Mueller M, Alam M. The primary structures of the Archaeon Halobacterium salinarium blue light receptor sensory rhodopsin II and its transducer, a methyl-accepting protein. Proc Natl Acad Sci U S A. 1996;93:8230-5 pubmed
    ..This paper describes the first example that both HtrI and HtrII exist in the same halobacterial cell, confirming that different sensory rhodopsins SRI and SRII in the same organism have their own distinct transducers...
  22. Muroda K, Nakashima K, Shibata M, Demura M, Kandori H. Protein-bound water as the determinant of asymmetric functional conversion between light-driven proton and chloride pumps. Biochemistry. 2012;51:4677-84 pubmed publisher
    ..We concluded that the cause of nonfunctional conversion of HR is the lack of strongly hydrogen-bonded water, the functional determinant of the proton pump. ..
  23. Furutani Y, Sudo Y, Kamo N, Kandori H. FTIR spectroscopy of the complex between pharaonis phoborhodopsin and its transducer protein. Biochemistry. 2003;42:4837-42 pubmed
    ..In addition, we observed D(2)O-insensitive bands at 3479 (-)/3369 (+) cm(-1) only in the presence of pHtrII, which presumably originate from an X-H stretch of an amino acid side chain inside the protein. ..
  24. Abilez O. Cardiac optogenetics. Conf Proc IEEE Eng Med Biol Soc. 2012;2012:1386-9 pubmed publisher
    ..For future therapy, in vivo optical stimulation could allow precise and specific synchronization of implanted hiPSC-CM with patient cardiac rates and rhythms. ..
  25. Hasegawa C, Kikukawa T, Miyauchi S, Seki A, Sudo Y, Kubo M, et al. Interaction of the halobacterial transducer to a halorhodopsin mutant engineered so as to bind the transducer: Cl- circulation within the extracellular channel. Photochem Photobiol. 2007;83:293-302 pubmed
  26. Tamogami J, Kikukawa T, Ikeda Y, Takemura A, Demura M, Kamo N. The photochemical reaction cycle and photoinduced proton transfer of sensory rhodopsin II (Phoborhodopsin) from Halobacterium salinarum. Biophys J. 2010;98:1353-63 pubmed publisher
    ..The analysis yielded a value of 7.5 for the pKa of X-H. The proton uptake and release occurred during M-decay and O-decay, respectively. ..
  27. Muneyuki E, Shibazaki C, Ohtani H, Okuno D, Asaumi M, Mogi T. Time-resolved measurements of photovoltage generation by bacteriorhodopsin and halorhodopsin adsorbed on a thin polymer film. J Biochem. 1999;125:270-6 pubmed
    ..measurement system and examined the photovoltage kinetics of wild-type bacteriorhodopsin, its D96N mutant, and halorhodopsins from Halobacterium salinarum and Natronobacterium pharaonis...
  28. Cisneros D, Oberbarnscheidt L, Pannier A, Klare J, Helenius J, Engelhard M, et al. Transducer binding establishes localized interactions to tune sensory rhodopsin II. Structure. 2008;16:1206-13 pubmed publisher
    ..These findings provide unique insights into molecular mechanisms that "prime" the complex for signaling, and guide the receptor toward transmitting light-activated structural changes to its cognate transducer. ..
  29. Hein M, Radu I, Klare J, Engelhard M, Siebert F. Consequences of counterion mutation in sensory rhodopsin II of Natronobacterium pharaonis for photoreaction and receptor activation: an FTIR study. Biochemistry. 2004;43:995-1002 pubmed
    ..The results are discussed with respect to the altered electrostatic interactions, role of proton transfer, the published 3D structure, and physiological activity...
  30. Abbott A. Proteins make light work of nerve control. Nature. 2007;446:588-9 pubmed
  31. Beuming T, Weinstein H. Modeling membrane proteins based on low-resolution electron microscopy maps: a template for the TM domains of the oxalate transporter OxlT. Protein Eng Des Sel. 2005;18:119-25 pubmed
    ..m.s.d. from their crystal structures. The protocol is applied to generate a model of the oxalate transporter OxlT, for which a high-resolution structure is not yet available. ..
  32. Gross M. Shining new light on the brain. Curr Biol. 2011;21:R831-3 pubmed
    ..Michael Gross reports. ..
  33. Felix Ortiz A, Beyeler A, Seo C, Leppla C, Wildes C, Tye K. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron. 2013;79:658-64 pubmed publisher
    ..These data establish a role for BLA-vHPC synapses in bidirectionally controlling anxiety-related behaviors in an immediate, yet reversible, manner and a model for the local circuit mechanism of BLA inputs in the vHPC. ..
  34. Furutani Y, Kandori H. Hydrogen-bonding changes of internal water molecules upon the actions of microbial rhodopsins studied by FTIR spectroscopy. Biochim Biophys Acta. 2014;1837:598-605 pubmed publisher
    ..We reviewed the results on dynamics of the internal water molecules in pharaonis halorhodopsin as well. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks. ..
  35. Mironova O, Budyak I, Büldt G, Schlesinger R, Heberle J. FT-IR difference spectroscopy elucidates crucial interactions of sensory rhodopsin I with the cognate transducer HtrI. Biochemistry. 2007;46:9399-405 pubmed
    ..We suggest that Asn53 plays a role similar to that of Asn74 of the HtrII from Natronobacterium pharaonis, the latter forming a hydrogen bond to the receptor within the membrane. ..
  36. Etzkorn M, Seidel K, Li L, Martell S, Geyer M, Engelhard M, et al. Complex formation and light activation in membrane-embedded sensory rhodopsin II as seen by solid-state NMR spectroscopy. Structure. 2010;18:293-300 pubmed publisher
    ..These latter protein segments, the inherent plasticity of the HAMP domain, and the observation of an extended SRII/HtrII membrane-embedded interface may be crucial components for optimal signal relay efficiency across the cell membrane. ..
  37. Iwasa T, Abe E, Yakura Y, Yoshida H, Kamo N. Tryptophan 171 in Pharaonis phoborhodopsin (sensory rhodopsin II) interacts with the chromophore retinal and its substitution with alanine or threonine slowed down the decay of M- and O-intermediate. Photochem Photobiol. 2007;83:328-35 pubmed
    ..In addition, the involvement of W171 in the hydrogen-bonding network is suggested by the O-decay. We also found that glycerol slowed the decay of M and not of O. ..
  38. Bordignon E, Klare J, Doebber M, Wegener A, Martell S, Engelhard M, et al. Structural analysis of a HAMP domain: the linker region of the phototransducer in complex with sensory rhodopsin II. J Biol Chem. 2005;280:38767-75 pubmed publisher
    ..Additionally, transducer-transducer and transducer-receptor proximity relations revealed the overall architecture of the AS-1 sequences in the 2:2 complex, which are suggested to form a molten globular type of a coiled-coil bundle...
  39. Iwamoto M, Sudo Y, Shimono K, Araiso T, Kamo N. Correlation of the O-intermediate rate with the pKa of Asp-75 in the dark, the counterion of the Schiff base of Pharaonis phoborhodopsin (sensory rhodopsin II). Biophys J. 2005;88:1215-23 pubmed
    ..The implications of these observations are discussed in detail. ..
  40. Furutani Y, Kamada K, Sudo Y, Shimono K, Kamo N, Kandori H. Structural changes of the complex between pharaonis phoborhodopsin and its cognate transducer upon formation of the M photointermediate. Biochemistry. 2005;44:2909-15 pubmed
  41. Golden S, Heshmati M, Flanigan M, Christoffel D, Guise K, Pfau M, et al. Basal forebrain projections to the lateral habenula modulate aggression reward. Nature. 2016;534:688-92 pubmed publisher
    ..These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing. ..
  42. Tateishi Y, Abe T, Tamogami J, Nakao Y, Kikukawa T, Kamo N, et al. Spectroscopic evidence for the formation of an N intermediate during the photocycle of sensory rhodopsin II (phoborhodopsin) from Natronobacterium pharaonis. Biochemistry. 2011;50:2135-43 pubmed publisher
    ..These observations allowed us to propose a structural model for a photocycle that involves N. ..
  43. Inoue K, Nomura Y, Kandori H. Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps. J Biol Chem. 2016;291:9883-93 pubmed publisher
    ..By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro. ..
  44. Iwamoto M, Sudo Y, Shimono K, Kamo N. Selective reaction of hydroxylamine with chromophore during the photocycle of pharaonis phoborhodopsin. Biochim Biophys Acta. 2001;1514:152-8 pubmed
    ..These findings reveal that water-soluble hydroxylamine reacts selectively with the M-intermediate and its implication was discussed...
  45. Kandori H, Kamo N. [Crystal structure of phoborhodopsin: mechanisms of color tuning and signal transduction]. Tanpakushitsu Kakusan Koso. 2002;47:620-5 pubmed
  46. Huang F, Tang B, Jiang H. Optogenetic investigation of neuropsychiatric diseases. Int J Neurosci. 2013;123:7-16 pubmed publisher
    ..We propose that novel optogenetics technology creates excellent opportunities for innovative treatment strategies of neuropsychiatric diseases. ..
  47. Kubicek J, Schlesinger R, Baeken C, Büldt G, Schafer F, Labahn J. Controlled in meso phase crystallization--a method for the structural investigation of membrane proteins. PLoS ONE. 2012;7:e35458 pubmed publisher
    ..3 Å resolution have been obtained in this approach. CIMP and the developed consumables and protocols have been successfully applied to obtain crystals of sensory rhodopsin II (SRII) from Halobacterium salinarum for the first time. ..
  48. Sato M, Kubo M, Aizawa T, Kamo N, Kikukawa T, Nitta K, et al. Role of putative anion-binding sites in cytoplasmic and extracellular channels of Natronomonas pharaonis halorhodopsin. Biochemistry. 2005;44:4775-84 pubmed
    ..The importance of Thr218 for binding of Cl(-) to the CP channel was indicated by these results. On the basis of these observations, the possible anion transport mechanism of NpHR was discussed...
  49. Kamada K, Furutani Y, Sudo Y, Kamo N, Kandori H. Temperature-dependent interactions between photoactivated pharaonis phoborhodopsin and its transducer. Biochemistry. 2006;45:4859-66 pubmed
    ..A molecular mechanism of protein structural changes in the ppR/pHtrII complex is discussed on the basis of the present FTIR results. ..
  50. Taniguchi Y, Ikehara T, Kamo N, Watanabe Y, Yamasaki H, Toyoshima Y. Application of fluorescence resonance energy transfer (FRET) to investigation of light-induced conformational changes of the phoborhodopsin/transducer complex. Photochem Photobiol. 2007;83:311-6 pubmed
  51. Dai G, Zhang Y, Tamogami J, Demura M, Kamo N, Kandori H, et al. An amino acid residue (S201) in the retinal binding pocket regulates the photoreaction pathway of phoborhodopsin. Biochemistry. 2011;50:7177-83 pubmed publisher
    ..Thus, the interaction between S201 and C14 might be the main factor affecting formation of P480...
  52. Sasaki T, Aizawa T, Kamiya M, Kikukawa T, Kawano K, Kamo N, et al. Effect of chloride binding on the thermal trimer-monomer conversion of halorhodopsin in the solubilized system. Biochemistry. 2009;48:12089-95 pubmed publisher
    ..8, 35.3, and 40.5 kcal/mol, respectively. The presence of a second chloride-binding site with a Hill coefficient of approximately 2 at the surface of NpHR to control the trimer-monomer conversion was discussed. ..
  53. Balashov S, Sumi M, Kamo N. The M intermediate of Pharaonis phoborhodopsin is photoactive. Biophys J. 2000;78:3150-9 pubmed
    ..Photoconversion of the M intermediate provides a possible pathway for photoreception in halobacteria and a useful tool for studying the mechanisms of signal transduction by phoborhodopsin (sensory rhodopsin II). ..