Channelrhodopsin

Channelrhodopsins are a subfamily of opsin proteins that function as light-gated ion channels.[1] They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis, i.e. movement in response to light. Expressed in cells of other organisms, they enable the use of light to control intracellular acidity, calcium influx, electrical excitability, and other cellular processes. Three channelrhodopsins are currently known: Channelrhodopsin-1 (ChR1), Channelrhodopsin-2 (ChR2), and Volvox Channelrhodopsin (VChR1). All known Channelrhodopsins are nonspecific cation channels, conducting H+, Na+, K+, and Ca2+ ions.

Contents

History

Channelrhodopsins were first discovered to be a single-component light-activated cation channel from the green algae Chlamydomonas reinhardtii by Georg Nagel and Peter Hegemann in 2002.[2] Channelrhodopsin-2 (ChR2), which was also isolated from Chlamydomonas reinhardtii, was similarly discovered by Peter Hegemann's group in 2001, and submitted directly to GenBank,[3] before being characterized by Georg Nagel's group and discovered independently by John Spudich's group in 2002.[4] In collaboration with Peter Hegemann, along with Ernst Bamberg and with Georg Nagel as first and corresponding author, it was demonstrated that channelrhodopsin-2 is also a directly light-gated ion channel like ChR1.[5] In 2005, three groups sequentially established ChR2 as a tool for genetically targeted optical remote control (optogenetics) of neurons, neural circuits and behavior. At first, Karl Deisseroth's lab (in a paper published in August 2005) demonstrated that ChR2 could be deployed to control mammalian neurons in vitro, achieving temporal precision on the order of milliseconds (both, in terms of delay to spiking, as well as in terms of temporal jitter).[6] This was a significant finding, since firstly, all opsins (microbial as well as vertebrate) require retinal as the light-sensing co-factor, and it was unclear, if central mammalian nerve cells would contain sufficient retinal levels - but surprisingly, they do. Secondly, it showed despite the small single-channel conductance, sufficient potency to drive mammalian neurons above action potential threshold. Thirdly, it demonstrated channelrhodopsin to be the first optogenetic tool, with which neural activity could be controlled with the temporal precision at which neurons operate (a few milliseconds); an earlier tool for photostimulation, cHARGe, demonstrated proof of principle in cultured neurons but was never usable [7] since it operated with a precision on the order of seconds, was highly variable, and did not allow control of individual action potentials. Five months later (December 2005), a second study was published by Peter Hegemann's and Stefan Herlitze's groups confirming the ability of ChR2 to control the activity of vertebrate neurons, at this time in the chick spinal cord.[8] This study was also the first, where ChR2 was expressed alongside an optical silencer, vertebrate rhodopsin-4 in this case, demonstrating for the first time, that excitable cells could be activated and silenced using these two tools simultaneously, but illuminating the tissue at different wavelengths. In the same month, the groups of Alexander Gottschalk and Ernst Bamberg (with Georg Nagel taking the experimental lead) demonstrated that ChR2, if expressed in specific neurons or muscle cells, can evoke predictable behaviours, i.e. can control the nervous system of an intact animal, which in this case was the invertebrate C. elegans.[9] This was the first study, using the remote control via ChR2 to steer the behaviour of an animal. And it was also the first study, that deployed ChR2 for an optogenetic experiment - i.e. that rendered genetically specified cell types subject to optical remote control, while the other two studies, did not specifically target ChR2 expression genetically. Although both aspects had been illustrated earlier that year by another group, the Miesenböck lab, deploying the indirectly light-gated ion channel P2X2,[10] it was henceforth microbial opsins like channelrhodopsin that dominated the field of genetically targeted remote control of excitable cells, due to the power, speed, targetability, ease of use, and temporal precision of direct optical activation, not requiring any external chemical compound such as caged ligands.[11]

To overcome its principle downsides - the small single-channel conductance (especially in steady-state), the fixation on one optimal excitation wavelength (~470 nm, blue) as well as the relatively long recovering time, not permitting controlled firing of neurons above 20–40 Hz - ChR2 has been optimized using genetic engineering: The first optimization involved the point mutation H134R (exchanging the amino acid Histidine in position 134 of the native protein for an Arginine), and published in the same paper, that established ChR2 as an optogenetic tool in C. elegans.[9] Further improvements were mainly carried by the close collaboration between the groups of Peter Hegemann and Karl Deisseroth. They included the introduction of the point mutation C128S, which made the resulting ChR2-derivative a step-function tool, that stays in the open state once "switched on" by blue light, until it is switched off by yellow light - a modification that deteriorates temporal precision, but greatly increases light sensitivity (by two orders of magnitude).[12] One year later (2010) the same authors introduced another mutation into the native molecule, E123T, yielding the ChR2-derivative ChETA, which does not only feature a higher single-channel conductance (in the desensitized/steady state), but also a much faster on- and off-kinetics, permitting the control of individual action potentials at frequencies of at least up to 200 Hz (in appropriate cell types).[13] Even before these achievements, Roger Tsien's lab had also optimized ChR2 towards the same direction (higher steady-state conductance), by creating chimeras of ChR1 and ChR2 and mutating them at decisive amino acids, yielding the tools ChEF and ChIEF.[14] Finally, the groups of Hegemann and Deisseroth discovered VChR1 in the multicellular algae Volvox carteri, and thus provided a tool - comparable to ChR2 - but with a red-shifted absorption spectrum, thus allowing excitation of two distinct cell populations at two distinct wavelengths.[15]

Karl Deisseroth's group has also taken the lead in developing optimal viral vectors for genetic targeting of ChR2 and its derivatives, thereby pioneering many optogenetic applications in actual experiments, alone or in collaboration, including the genetically targeted remote control in rodents in vivo,[16] the optogenetic induction of learning in rodents,[17] the experimental treatment of Parkinson's disease in rats,[18][19] the combination with imaging (all-optical systems)[20] and the combination with fMRI (opto-fMRI).[21] Other labs have pioneered essential applications of ChR2 in paradigms such as the mapping of long-range[22] and local[23] neural circuits, its expression from a transgenic locus - directly[24] or in the Cre-lox conditional paradigm[23] - as well as the two-photon excitation of ChR2, permitting the activation of individual cells.[25][26][27]

Structure

Structurally, channelrhodopsins are retinylidene proteins. They are seven-transmembrane proteins like rhodopsin, and contain the light-isomerizable chromophore all-trans-retinal (an aldehyde derivative of vitamin A). The retinal chromophore is covalently linked to the rest of the protein via a protonated Schiff base. Whereas most 7-transmembrane proteins are G protein-coupled receptors that open other ion channels indirectly via second messengers (i.e. they are metabotropic), channelrhodopsins directly form ion channels (i.e. they are ionotropic).[1] This makes cellular depolarization extremely fast, robust, and useful for bioengineering and neuroscience applications, including photostimulation.

Function

Scheme of ChR2-RFP fusion construct

ChR2 absorbs blue light with an absorption and action spectrum maximum at 480 nm.[28] When the all-trans-retinal complex absorbs a photon, it induces a conformational change from all-trans to 13-cis-retinal. This conformational change introduces a further conformational change in the transmembrane protein, opening the pore to at least 6Å. Within a few milliseconds, the retinal relaxes back to the all-trans form, closing the pore and stopping the flow of ions.[1]

Designer-Channelrhodopsins

The C-terminal end of Channelrhodopsin-2 extends into the intracellular space and can be replaced by fluorescent proteins without affecting channel function. This kind of fusion construct can be very useful to visualize the morphology of ChR2 expressing cells.[29][30] Channel kinetics can be modified by point mutations close to the retinal binding pocket. For example, closing of the channel after optical activation can be substantially delayed by mutating a specific protein residue, C128. This modification results in a super-sensitive Channelrhodopsin that can be opened by a blue light pulse and closed by a green or yellow light pulse.[31][32] Mutating the E123 residue accelerates channel kinetics, and the resulting ChR2 mutants have been used to spike neurons at up to 200 Hz.[33] T159 mutants display increased photocurrents, and a combination of T159 and E123 (ET/TC) is both faster and more powerful than the original ChR2.[34] In the future, directed molecular engineering might also be applied to develop channelrhodopsins with altered spectral sensitivity.

Applications

Channelrhodopsins can be readily expressed in excitable cells such as neurons using a variety of transfection techniques (viral transfection, electroporation, gene gun). The light absorbing pigment retinal is already present in most cells (of vertebrates) in the form of Vitamin A. This makes depolarization of excitable cells very straightforward, useful for many bioengineering and neuroscience applications such as photostimulation of neurons for probing of neural circuits.[29] The blue-light sensitive ChR2 and the yellow light-activated chloride pump halorhodopsin together enable multiple-color optical activation and silencing of neural activity with millisecond precision.[35][36] VChR1 form from the colonial alga Volvox carteri absorbs maximally at 535 nm and had been used to stimulate cells with yellow light (580 nm).[37] The emerging field of controlling networks of genetically modified cells with light has been termed Optogenetics.

Using fluorescently labeled ChR2, light-stimulated axons and synapses can be identified in intact brain tissue.[30] This is useful to study the molecular events during the induction of synaptic plasticity.[38] ChR2 has also been used to map long-range connections from one side of the brain to the other, and to map the spatial location of specific inputs on the dendritic tree of individual neurons.[39][40]

The behavior of transgenic animals expressing ChR2 in subpopulations of neurons can be remote-controlled by intense blue light. This has been demonstrated in nematodes, fruit flies, zebrafish, and in mice.[41][42] Visual function in blind mice can be partially restored by expressing ChR2 in inner retinal cells.[43][44] In the future, ChR2 might also find medical applications, e.g. in certain forms of retinal degeneration or for deep brain stimulation.

References

  1. ^ a b c Nagel G, Szellas T, Huhn W, et al. (November 25, 2003). "Channelrhodopsin-2, a directly light-gated cation-selective membrane channel". Proc. Natl. Acad. Sci. U.S.A. 100 (24): 13940–5. doi:10.1073/pnas.1936192100. PMC 283525. PMID 14615590. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=283525. 
  2. ^ Nagel G, Ollig D, Fuhrmann M, et al. (June 28, 2002). "Channelrhodopsin-1: a light-gated proton channel in green algae". S cience 296 (5577): 2395–8. doi:10.1126/science.1072068. PMID 12089443. 
  3. ^ Kateriya, S. Fuhrmann, M. Hegemann, P.: Direct Submission: Chlamydomonas reinhardtii retinal binding protein (cop4) gene; GenBank accession number AF461397
  4. ^ Sineshchekov, O.A., Jung, K.H., and Spudich, J.L. (2002). Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. Proc Natl Acad Sci U S A 99, 8689-8694.
  5. ^ Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., and Bamberg, E. (2003). Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100, 13940-13945.
  6. ^ Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G., and Deisseroth, K. (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8, 1263-1268.
  7. ^ Zemelman, B.V., Lee, G.A., Ng, M., and Miesenböck, G. (2002). Selective photostimulation of genetically chARGed neurons. Neuron 33, 15-22.
  8. ^ Li, X., Gutierrez, D.V., Hanson, M.G., Han, J., Mark, M.D., Chiel, H., Hegemann, P., Landmesser, L.T., and Herlitze, S. (2005). Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci U S A 102, 17816-17821.
  9. ^ a b Nagel, G., Brauner, M., Liewald, J.F., Adeishvili, N., Bamberg, E., and Gottschalk, A. (2005). Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr Biol 15, 2279-2284.
  10. ^ Lima, S.Q., and Miesenböck, G. (2005). Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121, 141-152.
  11. ^ Zhang, F., Wang, L.P., Boyden, E.S., and Deisseroth, K. (2006). Channelrhodopsin-2 and optical control of excitable cells. Nat Methods 3, 785-792.
  12. ^ Berndt, A., Yizhar, O., Gunaydin, L.A., Hegemann, P., and Deisseroth, K. (2009). Bi-stable neural state switches. Nat Neurosci 12, 229-234.
  13. ^ Gunaydin, L.A., Yizhar, O., Berndt, A., Sohal, V.S., Deisseroth, K., and Hegemann, P. (2010). Ultrafast optogenetic control. Nat Neurosci 13, 387-392.
  14. ^ Lin, J.Y., Lin, M.Z., Steinbach, P., and Tsien, R.Y. (2009). Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys J 96, 1803-1814.
  15. ^ Zhang, F., Prigge, M., Beyriere, F., Tsunoda, S.P., Mattis, J., Yizhar, O., Hegemann, P., and Deisseroth, K. (2008). Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat Neurosci 11, 631-633.
  16. ^ Adamantidis, A.R., Zhang, F., Aravanis, A.M., Deisseroth, K., and de Lecea, L. (2007). Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450, 420-424.
  17. ^ Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G.D., Bonci, A., de Lecea, L., and Deisseroth, K. (2009). Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning. Science 324, 1080-1084.
  18. ^ Gradinaru, V., Mogri, M., Thompson, K.R., Henderson, J.M., and Deisseroth, K. (2009). Optical Deconstruction of Parkinsonian Neural Circuitry. Science 324, 354-359.
  19. ^ Kravitz, A.V., Freeze, B.S., Parker, P.R.L., Kay, K., Thwin, M.T., Deisseroth, K., and Kreitzer, A.C. (2010). Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622-626.
  20. ^ Zhang, F., Wang, L.P., Brauner, M., Liewald, J.F., Kay, K., Watzke, N., Wood, P.G., Bamberg, E., Nagel, G., Gottschalk, A., and Deisseroth, K. (2007). Multimodal fast optical interrogation of neural circuitry. Nature 446, 633-639.
  21. ^ Lee, J.H., Durand, R., Gradinaru, V., Zhang, F., Goshen, I., Kim, D.S., Fenno, L.E., Ramakrishnan, C., and Deisseroth, K. (2010). Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature 465, 788-792.
  22. ^ Petreanu, L., Huber, D., Sobczyk, A., and Svoboda, K. (2007). Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections. Nat Neurosci 10, 663-668.
  23. ^ a b Kätzel, D., Zemelman, B.V., Buetfering, C., Wölfel, M., and Miesenböck, G. (2011). The columnar and laminar organization of inhibitory connections to neocortical excitatory cells. Nat Neurosci 14, 100-107.
  24. ^ Wang, H. Peca, J. Matsuzaki, M. Matsuzaki, K. Noguchi, J. Qiu, L. Wang, D. Zhang, F. Boyden, E. Deisseroth, K. Kasai, H. Hall, W. C. Feng, G. Augustine, G. J. (2007). High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice. Proceedings of the National Academy of Sciences 104, 8143-8148.
  25. ^ Mohanty, S.K., Reinscheid, R.K., Liu, X., Okamura, N., Krasieva, T.B., and Berns, M.W. (2008). In-depth activation of channelrhodopsin 2-sensitized excitable cells with high spatial resolution using two-photon excitation with a near-infrared laser microbeam. Biophys J 95, 3916-3926.
  26. ^ Rickgauer, J.P., and Tank, D.W. (2009). Two-photon excitation of channelrhodopsin-2 at saturation. Proceedings of the National Academy of Sciences 106, 15025-15030.
  27. ^ Andrasfalvy, B.K., Zemelman, B.V., Tang, J., and Vaziri, A. (2010). Two-photon single-cell optogenetic control of neuronal activity by sculpted light. Proc Natl Acad Sci U S A 107, 11981-11986.
  28. ^ Christian Bamann, Taryn Kirsch, Georg Nagel, Ernst Bamberg (2008). "Spectral Characteristics of the Photocycle of Channelrhodopsin-2 and Its Implication for Channel Function". J Mol Biol. 375 (3): 686–694. doi:10.1016/j.jmb.2007.10.072. PMID 18037436. 
  29. ^ a b Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., and Deisseroth, K. (2005). "Millisecond-timescale, genetically-targeted optical control of neural activity". Nature Neuroscience 8 (9): 1263–1268. doi:10.1038/nn1525. PMID 16116447. 
  30. ^ a b Zhang YP, Oertner TG (February 4, 2007). "Optical induction of synaptic plasticity using a light-sensitive channel". Nat. Methods 4 (2): 139–41. doi:10.1038/nmeth988. PMID 17195846. 
  31. ^ Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (December 2, 2008). "Bi-stable neural state switches". Nat. Neuroscience 12 (2): 229–234. doi:10.1038/nn.2247. PMID 19079251. 
  32. ^ Schoenenberger P, Gerosa D, Oertner TO (December 4, 2009). Mansvelder, Huibert D.. ed. "Temporal Control of Immediate Early Gene Induction by Light". PLoS ONE 4 (12): e8185. doi:10.1371/journal.pone.0008185. PMC 2780714. PMID 19997631. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2780714. 
  33. ^ Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P (January 17, 2010). "Ultrafast optogenetic control". Nature Neuroscience 13 (3): 387–92. doi:10.1038/nn.2495. PMID 20081849. 
  34. ^ Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K, Hegemann P, Oertner TG (May 3, 2011). "High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels". Proc Natl Acad Sci USA 108 (18): 7595–7600. doi:10.1073/pnas.1017210108. PMC 3088623. PMID 21504945. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3088623. 
  35. ^ Han X, Boyden ES (March 21, 2007). Rustichini, Aldo. ed. "Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution". PLoS ONE 2 (3): e299. doi:10.1371/journal.pone.0000299. PMC 1808431. PMID 17375185. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1808431. 
  36. ^ Zhang F, Wang LP, Brauner M, et al. (April 5, 2007). "Multimodal fast optical interrogation of neural circuitry". Nature 446 (7136): 633–9. doi:10.1038/nature05744. PMID 17410168. 
  37. ^ Zhang F, Prigge M, Beyrière F, et al. (April 23, 2008). "Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri". Nat. Neurosci. 11 (6): 631–3. doi:10.1038/nn.2120. PMC 2692303. PMID 18432196. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2692303. 
  38. ^ Zhang YP, Holbro N, Oertner TG (August 19, 2008). "Optical induction of plasticity at single synapses reveals input-specific accumulation of αCaMKII". Proc. Natl. Acad. Sci. U.S.A. 105 (33): 12039–44. doi:10.1073/pnas.0802940105. PMC 2575337. PMID 18697934. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2575337. 
  39. ^ Petreanu L, Huber D, Sobczyk A, Svoboda K (May 1, 2007). "Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections". Nat. Neurosci. 10 (5): 663–8. doi:10.1038/nn1891. PMID 17435752. 
  40. ^ Petreanu L, Mao Y, Sternson SM, Svoboda K (Feb 26, 2009). "The subcellular organization of neocortical excitatory connections". Nature 457 (7233): 1142–5. doi:10.1038/nature07709. PMC 2745650. PMID 19151697. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2745650. 
  41. ^ Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F (August 5, 2008). "Escape Behavior Elicited by Single, Channelrhodopsin-2-Evoked Spikes in Zebrafish Somatosensory Neurons". Current Biology 18 (15): 1133–7. doi:10.1016/j.cub.2008.06.077. PMC 2891506. PMID 18682213. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2891506. 
  42. ^ Huber D, Petreanu L, Ghitani N, Ranade S, Hromádka T, Mainen Z, Svoboda K (January 3, 2008). "Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice". Nature 451 (7174): 61–4. doi:10.1038/nature06445. PMID 18094685. 
  43. ^ Bi A, Cui J, Ma YP, “et al.” (April 2006). "Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration". Neuron 50 (1): 23–33. doi:10.1016/j.neuron.2006.02.026. PMC 1459045. PMID 16600853. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1459045. 
  44. ^ Lagali PS, Balya D, Awatramani GB, et al. (June 1, 2008). "Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration". Nat. Neurosci. 11 (6): 667–75. doi:10.1038/nn.2117. PMID 18432197. 

Further reading

External links


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Channelrhodopsin — Bezeichner Gen Name(n) ChR1, ChR2, VChR1 …   Deutsch Wikipedia

  • channelrhodopsin — noun An opsin protein that controls phototaxis in unicellular green algae …   Wiktionary

  • Kanalrhodopsin — Channelrhodopsin Bezeichner Gen Name(n) ChR1, ChR2, VChR1 Transporter Klassifikation …   Deutsch Wikipedia

  • Optogenetics — Neuropsychology Topics Brain computer interface …   Wikipedia

  • Optogenetik — Die Optogenetik ist ein relativ neues Fachgebiet, das sich mit der Kontrolle von genetisch modifizierten Zellen mittels Licht beschäftigt. Inhaltsverzeichnis 1 Beschreibung 2 Channelrhodopsin als Beispiel für einen optogenetischen Schalter 3 …   Deutsch Wikipedia

  • Light-gated ion channel — Light gated ion channels are a group of transmembrane proteins that form ion channels; pores which open or close in response to light. Most light gated ion channels have been synthesized in the laboratory for study, though one naturally occurring …   Wikipedia

  • Photostimulation — is the use of light to artificially activate biological compounds, cells, or even whole organisms. Photostimulation can be used to noninvasively probe the causal relationships between different biological processes, using only light. In the long… …   Wikipedia

  • Halorhodopsin — is a light driven ion pump, specific for chloride ions, and found in phylogenetically ancient bacteria (archaea), known as halobacteria. It is a seven transmembrane protein of the retinylidene protein family, homologous to the light driven proton …   Wikipedia

  • Rhodopsin — Rhodopsin, also known as visual purple, is a pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G protein coupled receptor family… …   Wikipedia

  • Sehpurpur — Rhodopsin Dreidimensionale Struktur des Backbones von Rhodopsin. In der Mitte ist das für die Signalkaskade wichtige 11 cis Retinal …   Deutsch Wikipedia


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.