1932

Abstract

Channelrhodopsins (ChRs) are directly light-gated ion channels that function as sensory photoreceptors in flagellated green algae, allowing these algae to identify optimal light conditions for growth. In neuroscience, ChRs constitute the most versatile tools for the light-induced activation of selected cells or cell types with unprecedented precision in time and space. In recent years, many ChR variants have been discovered or engineered, and countless electrical and spectroscopic studies of these ChRs have been carried out, both in host cells and on purified recombinant proteins. With significant support from a high-resolution 3D structure and from molecular dynamics calculations, scientists are now able to develop models that conclusively explain ChR activation and ion conductance on the basis of chromophore isomerization, structural changes, proton transfer reactions, and water rearrangement on timescales ranging from femtoseconds to minutes.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-060414-034014
2015-06-22
2024-10-15
Loading full text...

Full text loading...

/deliver/fulltext/biophys/44/1/annurev-biophys-060414-034014.html?itemId=/content/journals/10.1146/annurev-biophys-060414-034014&mimeType=html&fmt=ahah

Literature Cited

  1. Arenkiel BR, Peca J, Davison IG, Feliciano C, Deisseroth K. 1.  et al. 2007. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54:2205–18 [Google Scholar]
  2. Babitzki G, Denschlag R, Tavan P. 2.  2009. Polarization effects stabilize bacteriorhodopsin's chromophore binding pocket: a molecular dynamics study. J. Phys. Chem. B 113:3010483–95 [Google Scholar]
  3. Bamann C, Gueta R, Kleinlogel S, Nagel G, Bamberg E. 3.  2010. Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond. Biochemistry 49:2267–78 [Google Scholar]
  4. Bamann C, Kirsch T, Nagel G, Bamberg E. 4.  2008. Spectral characteristics of the photocycle of channelrhodopsin-2 and its implication for channel function. J. Mol. Biol. 375:3686–94 [Google Scholar]
  5. Berndt A, Lee SY, Ramakrishnan C, Deisseroth K. 5.  2014. Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344:420–24 [Google Scholar]
  6. Berndt A, Prigge M, Gradmann D, Hegemann P. 6.  2010. Two open states with progressive proton selectivities in the branched channelrhodopsin-2 photocycle. Biophys. J. 98:5753–61 [Google Scholar]
  7. Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K. 7.  et al. 2011. High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. PNAS 108:187595–600 [Google Scholar]
  8. Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K. 8.  2009. Bi-stable neural state switches. Nat. Neurosci. 12:2229–34 [Google Scholar]
  9. Bi A, Cui J, Ma Y-P, Olshevskaya E, Pu M. 9.  et al. 2006. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:123–33 [Google Scholar]
  10. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. 10.  2005. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8:91263–68 [Google Scholar]
  11. Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F. 11.  2008. Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons. Curr. Biol. 18:151133–37 [Google Scholar]
  12. Doyle DA. 12.  1998. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:536069–77 [Google Scholar]
  13. Eisenhauer K, Kuhne J, Ritter E, Berndt A, Wolf S. 13.  et al. 2012. In channelrhodopsin-2 glu-90 is crucial for ion selectivity and is deprotonated during the photocycle. J. Biol. Chem. 287:96904–11 [Google Scholar]
  14. Ernst OP, Sánchez Murcia PA, Daldrop P, Tsunoda SP, Kateriya S, Hegemann P. 14.  2008. Photoactivation of channelrhodopsin. J. Biol. Chem. 283:31637–43 [Google Scholar]
  15. Foster KW, Smyth RD. 15.  1980. Light antennas in phototactic algae. Microbiol. Rev. 44:4572–630 [Google Scholar]
  16. Garczarek F, Gerwert K. 16.  2006. Polarized FTIR spectroscopy in conjunction with in situ H/D exchange reveals the orientation of protein internal carboxylic acids. J. Am. Chem. Soc. 128:128–29 [Google Scholar]
  17. Govorunova EG, Sineshchekov OA, Li H, Janz R, Spudich JL. 17.  2013. Characterization of a highly efficient blue-shifted channelrhodopsin from the marine alga Platymonas subcordiformis. J. Biol. Chem. 288:29911–22 [Google Scholar]
  18. Govorunova EG, Spudich EN, Lane CE, Sineshchekov OA, Spudich JL. 18.  2011. New channelrhodopsin with a red-shifted spectrum and rapid kinetics from Mesostigma viride. mBio 2:3e00115–11 [Google Scholar]
  19. Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. 19.  2009. Optical deconstruction of Parkinsonian neural circuitry. Science 324:5925354–59 [Google Scholar]
  20. Gradmann D, Berndt A, Schneider F, Hegemann P. 20.  2011. Rectification of the channelrhodopsin early conductance. Biophys. J. 101:51057–68 [Google Scholar]
  21. Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P. 21.  2010. Ultrafast optogenetic control. Nat. Neurosci. 13:3387–92 [Google Scholar]
  22. Hegemann P. 22.  2008. Algal sensory photoreceptors. Annu. Rev. Plant Biol. 59:167–89 [Google Scholar]
  23. Hegemann P, Ehlenbeck S, Gradmann D. 23.  2005. Multiple photocycles of channelrhodopsin. Biophys. J. 89:63911–18 [Google Scholar]
  24. Holland EM, Braun FJ, Nonnengässer C, Harz H, Hegemann P. 24.  1996. The nature of rhodopsin-triggered photocurrents in Chlamydomonas. I. Kinetics and influence of divalent ions. Biophys. J. 70:2924–31 [Google Scholar]
  25. Hou S-Y, Govorunova EG, Ntefidou M, Lane CE, Spudich EN. 25.  et al. 2011. Diversity of Chlamydomonas channelrhodopsins. Photochem. Photobiol. 88:1119–28 [Google Scholar]
  26. Hu JG, Sun BQ, Bizounok M, Hatcher ME, Lansing JC. 26.  et al. 1998. Early and late M intermediates in the bacteriorhodopsin photocycle: a solid-state NMR study. Biochemistry 37:228088–96 [Google Scholar]
  27. Ishizuka T, Kakuda M, Araki R, Yawo H. 27.  2006. Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels. Neurosci. Res. 54:285–94 [Google Scholar]
  28. Ito S, Kato HE, Taniguchi R, Iwata T, Nureki O, Kandori H. 28.  2014. Water-containing hydrogen-bonding network in the active center of channelrhodopsin. J. Am. Chem. Soc. 136:3475–82 [Google Scholar]
  29. Joh NH, Min A, Faham S, Whitelegge JP, Yang D. 29.  et al. 2008. Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins. Nature 453:71991266–70 [Google Scholar]
  30. Kateriya S. 30.  2004. “Vision” in single-celled algae. News Physiol. Sci. 19:3133–37 [Google Scholar]
  31. Kato HE, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T. 31.  et al. 2012. Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482:7385369–74 [Google Scholar]
  32. Kianianmomeni A, Stehfest K, Nematollahi G, Hegemann P, Hallmann A. 32.  2009. Channelrhodopsins of Volvox carteri are photochromic proteins that are specifically expressed in somatic cells under control of light, temperature, and the sex inducer. Plant Physiol. 151:1347–66 [Google Scholar]
  33. Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A. 33.  et al. 2014. Independent optical excitation of distinct neural populations. Nat. Methods 11:338–46 [Google Scholar]
  34. Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG. 34.  et al. 2011. Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh. Nat. Neurosci. 14:4513–18 [Google Scholar]
  35. Krause N, Engelhard C, Heberle J, Schlesinger R, Bittl R. 35.  2013. Structural differences between the closed and open states of channelrhodopsin-2 as observed by EPR spectroscopy. FEBS Lett. 587:203309–13 [Google Scholar]
  36. Kuhne J, Eisenhauer K, Ritter E, Hegemann P, Gerwert K, Bartl F. 36.  2014. Early formation of the ion-conducting pore in channelrhodopsin-2. Angew. Chemie Int. Ed. 54:4953–57 [Google Scholar]
  37. Li X, Gutierrez DV, Hanson MG, Han J, Mark MD. 37.  et al. 2005. Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. PNAS 102:4917816–21 [Google Scholar]
  38. Lin JY, Knutsen PM, Muller A, Kleinfeld D, Tsien RY. 38.  2013. ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat. Neurosci. 16:1499–508 [Google Scholar]
  39. Lin JY, Lin MZ, Steinbach P, Tsien RY. 39.  2009. Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys. J. 96:51803–14 [Google Scholar]
  40. Lórenz-Fonfría VA, Resler T, Krause N, Nack M, Gossing M. 40.  et al. 2013. Transient protonation changes in channelrhodopsin-2 and their relevance to channel gating. PNAS 110:14E1273–81 [Google Scholar]
  41. Luecke H, Schobert B, Lanyi JK, Spudich EN, Spudich JL. 41.  2001. Crystal structure of sensory rhodopsin II at 2.4 angstroms: insights into color tuning and transducer interaction. Science 293:55341499–503 [Google Scholar]
  42. Luecke H, Schobert B, Richter HT, Cartailler JP, Lanyi JK. 42.  1999. Structure of bacteriorhodopsin at 1.55 Å resolution. J. Mol. Biol. 291:4899–911 [Google Scholar]
  43. Mittelmeier TM, Boyd JS, Lamb MR, Dieckmann CL. 43.  2011. Asymmetric properties of the Chlamydomonas reinhardtii cytoskeleton direct rhodopsin photoreceptor localization. J. Cell Biol. 193:4741–53 [Google Scholar]
  44. Müller M, Bamann C, Bamberg E, Kühlbrandt W. 44.  2011. Projection structure of channelrhodopsin-2 at 6 Å resolution by electron crystallography. J. Mol. Biol. 414:186–95 [Google Scholar]
  45. Müller M, Bamann C, Bamberg E, Kühlbrandt W. 457  2014. Light-induced helix movements in channelrhodopsin-2. J. Mol. Biol. 427:2341–49 [Google Scholar]
  46. Nagel G, Brauner M, Liewald JF, Adeishvili N, Bamberg E, Gottschalk A. 46.  2005. Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr. Biol. 15:242279–84 [Google Scholar]
  47. Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM. 47.  et al. 2002. Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:55772395–98 [Google Scholar]
  48. Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N. 48.  et al. 2003. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. PNAS 100:2413940–45 [Google Scholar]
  49. Neumann-Verhoefen M-K, Neumann K, Bamann C, Radu I, Heberle J. 49.  et al. 2013. Ultrafast infrared spectroscopy on channelrhodopsin-2 reveals efficient energy transfer from the retinal chromophore to the protein. J. Am. Chem. Soc. 135:186968–76 [Google Scholar]
  50. Nikolic K, Degenaar P, Toumazou C. 50.  2006. Modeling and engineering aspects of channelrhodopsin2 system for neural photostimulation. Proc. Int. Conf. IEEE Eng. Med. Biol. Soc., 28th, New York1626–29 Piscataway, NJ: IEEE [Google Scholar]
  51. Nikolic K, Grossman N, Grubb MS, Burrone J, Toumazou C, Degenaar P. 51.  2009. Photocycles of channelrhodopsin-2. Photochem. Photobiol. 85:1400–11 [Google Scholar]
  52. Pan Z-H, Ganjawala TH, Lu Q, Ivanova E, Zhang Z. 52.  2014. ChR2 mutants at L132 and T159 with improved operational light sensitivity for vision restoration. PLOS ONE 9:6e98924 [Google Scholar]
  53. Patzelt H, Simon B, terLaak A, Kessler B, Kühne R. 53.  et al. 2002. The structures of the active center in dark-adapted bacteriorhodopsin by solution-state NMR spectroscopy. PNAS 99:159765–70 [Google Scholar]
  54. Petreanu L, Huber D, Sobczyk A, Svoboda K. 54.  2007. Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections. Nat. Neurosci. 10:5663–68 [Google Scholar]
  55. Plazzo AP, De Franceschi N, Da Broi F, Zonta F, Sanasi MF. 55.  et al. 2012. Bioinformatic and mutational analysis of channelrhodopsin-2 protein cation-conducting pathway. J. Biol. Chem. 287:74818–25 [Google Scholar]
  56. Prakash R, Yizhar O, Grewe B, Ramakrishnan C, Wang N. 56.  et al. 2012. Two-photon optogenetic toolbox for fast inhibition, excitation and bistable modulation. Nat. Methods 9:1171–79 [Google Scholar]
  57. Prigge M, Schneider F, Tsunoda SP, Shilyansky C, Wietek J. 57.  et al. 2012. Color-tuned channelrhodopsins for multiwavelength optogenetics. J. Biol. Chem. 287:31804–12 [Google Scholar]
  58. Radu I, Bamann C, Nack M, Nagel G, Bamberg E, Heberle J. 58.  2009. Conformational changes of channelrhodopsin-2. J. Am. Chem. Soc. 131:217313–19 [Google Scholar]
  59. Ritter E, Piwowarski P, Hegemann P, Bartl FJ. 59.  2013. Light-dark adaptation of channelrhodopsin C128T mutant. J. Biol. Chem. 288:1510451–58 [Google Scholar]
  60. Ritter E, Stehfest K, Berndt A, Hegemann P, Bartl FJ. 60.  2008. Monitoring light-induced structural changes of Channelrhodopsin-2 by UV-visible and Fourier transform infrared spectroscopy. J. Biol. Chem. 283:5035033–41 [Google Scholar]
  61. Ruffert K, Himmel B, Lall D, Bamann C, Bamberg E. 61.  et al. 2011. Glutamate residue 90 in the predicted transmembrane domain 2 is crucial for cation flux through channelrhodopsin 2. Biochem. Biophys. Res. Commun. 410:4737–43 [Google Scholar]
  62. Sattig T, Rickert C, Bamberg E, Steinhoff H-J, Bamann C. 62.  2013. Light-induced movement of the transmembrane helix b in channelrhodopsin-2. Angew. Chem. Int. Ed. Engl. 52:379705–8 [Google Scholar]
  63. Schneider F, Gradmann D, Hegemann P. 63.  2013. Ion selectivity and competition in channelrhodopsins. Biophys. J. 105:191–100 [Google Scholar]
  64. Scholz F, Bamberg E, Bamann C, Wachtveitl J. 64.  2012. Tuning the primary reaction of channelrhodopsin-2 by imidazole, pH, and site-specific mutations. Biophys. J. 102:112649–57 [Google Scholar]
  65. Schroll C, Riemensperger T, Bucher D, Ehmer J, Völler T. 65.  et al. 2006. Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae. Curr. Biol. 16:171741–47 [Google Scholar]
  66. Shimano T, Fyk-Kolodziej B, Mirza N, Asako M, Tomoda K. 66.  et al. 2013. Assessment of the AAV-mediated expression of channelrhodopsin-2 and halorhodopsin in brainstem neurons mediating auditory signaling. Brain Res. 1511:138–52 [Google Scholar]
  67. Sineshchekov OA, Govorunova EG, Wang J, Li H, Spudich JL. 67.  2013. Intramolecular proton transfer in channelrhodopsins. Biophys. J. 104:4807–17 [Google Scholar]
  68. Sineshchekov OA, Jung K-H, Spudich JL. 68.  2002. Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. PNAS 99:138689–94 [Google Scholar]
  69. Stehfest K, Hegemann P. 69.  2010. Evolution of the channelrhodopsin photocycle model. ChemPhysChem 11:61120–26 [Google Scholar]
  70. Stehfest K, Ritter E, Berndt A, Bartl F, Hegemann P. 70.  2010. The branched photocycle of the slow-cycling channelrhodopsin-2 mutant C128T. J. Mol. Biol. 398:5690–702 [Google Scholar]
  71. Sugiyama Y, Wang H, Hikima T, Sato M, Kuroda J. 71.  et al. 2009. Photocurrent attenuation by a single polar-to-nonpolar point mutation of channelrhodopsin-2. Photochem. Photobiol. Sci. 8:3328–36 [Google Scholar]
  72. Suzuki T, Yamasaki K, Fujita S, Oda K, Iseki M. 72.  et al. 2003. Archaeal-type rhodopsins in Chlamydomonas: model structure and intracellular localization. Biochem. Biophys. Res. Commun. 301:3711–17 [Google Scholar]
  73. Tsunoda SP, Hegemann P. 73.  2009. Glu 87 of channelrhodopsin-1 causes pH-dependent color tuning and fast photocurrent inactivation. Photochem. Photobiol. 85:2564–69 [Google Scholar]
  74. Ullrich S, Gueta R, Nagel G. 74.  2012. Degradation of channelopsin-2 in the absence of retinal and degradation resistance in certain mutants. Biol. Chem. 394:271–80 [Google Scholar]
  75. Verhoefen M-K, Bamann C, Blöcher R, Förster U, Bamberg E, Wachtveitl J. 75.  2010. The photocycle of channelrhodopsin-2: ultrafast reaction dynamics and subsequent reaction steps. ChemPhysChem 11:143113–22 [Google Scholar]
  76. Wang H, Sugiyama Y, Hikima T, Sugano E, Tomita H. 76.  et al. 2009. Molecular determinants differentiating photocurrent properties of two channelrhodopsins from Chlamydomonas. J. Biol. Chem. 284:95685–96 [Google Scholar]
  77. Watanabe HC, Welke K, Schneider F, Tsunoda S, Zhang F. 77.  et al. 2012. Structural model of channelrhodopsin. J. Biol. Chem. 287:107456–66 [Google Scholar]
  78. Watanabe HC, Welke K, Sindhikara DJ, Hegemann P, Elstner M. 78.  2013. Towards an understanding of channelrhodopsin function: simulations lead to novel insights of the channel mechanism. J. Mol. Biol. 425:1795–814 [Google Scholar]
  79. Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H. 79.  et al. 2014. Conversion of channelrhodopsin into a light-gated chloride channel. Science 344:409–12 [Google Scholar]
  80. Williams JC, Xu J, Lu Z, Klimas A, Chen X. 80.  et al. 2013. Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model. PLOS Comput. Biol. 9:e1003220 [Google Scholar]
  81. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ. 81.  et al. 2011. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:7363171–78 [Google Scholar]
  82. Zhang F, Prigge M, Beyrière F, Tsunoda SP, Mattis J. 82.  et al. 2008. Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat. Neurosci. 11:6631–33 [Google Scholar]
  83. Zhang F, Vierock J, Yizhar O, Fenno LE, Tsunoda S. 83.  et al. 2011. The microbial opsin family of optogenetic tools. Cell 147:71446–57 [Google Scholar]
  84. Zhang Y-P, Oertner TG. 84.  2007. Optical induction of synaptic plasticity using a light-sensitive channel. Nat. Methods 4:2139–41 [Google Scholar]
/content/journals/10.1146/annurev-biophys-060414-034014
Loading
/content/journals/10.1146/annurev-biophys-060414-034014
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error