Anion-conducting channelrhodopsin

Anion-conducting channelrhodopsins are ion channels that conduct negatively charged ions (such as chloride) and are directly gated by light, using retinal as light-sensitive pigment. The first anion-conducting channelrhodopsins were engineered from the cation-conducting Channelrhodopsin-2 by removing negatively charged amino acids from the channel pore. Naturally occurring anion-conducting channelrhodopsins were later identified in two species of cryptophyte algae (Guillardia theta, Proteomonas sulcata). Anion-conducting channelrhodopsins have been used to suppress the activity of specific neurons in mice.

Variants

name species absoption reference
slowChloC Chlamydomonas reinhardtii blue Wietek et al. 2014[1]
iC1C2 Chlamydomonas reinhardtii blue Berndt et al. 2014[2]
iChloC Chlamydomonas reinhardtii blue Wietek et al. 2015[3] in vivo inhibition
GtACR1 Guillardia theta blue Govorunova et al. 2015[4] large currents
SwiChR++ Chlamydomonas blue on / red off Berndt et al. 2016[5] bistable
PsACR1 Proteomonas sulcata green Wietek et al. 2016,[6] Govorunova et al. 2016[7]

Applications

Anion-conducting channelrhodopsins have been used as optogenetic tools to inhibit neuronal activation. When expressed in nerve cells, anion-conducting channelrhodopsins act as light-gated chloride channels. Their effect on the activity of the neuron is comparable to GABAA receptors, ligand-gated chloride channels found in inhibitory synapses: As the chloride concentration in mature neurons is very low, illumination results in an inward flux of negatively charged ions, clamping the neuron at the chloride reversal potential (- 65 mV). Under these conditions, excitatory synaptic inputs are not able to depolarize the neuron, preventing the initiation of action potentials. Axon terminals, however, have a higher chloride concentration and are therefore excited by ACRs.[8]

Further reading

Research highlight: A better way to turn off neurons[9]

Perspective: Expanding the optogenetics toolkit[10]

References

  1. Wietek, Jonas; Wiegert, J. Simon; Adeishvili, Nona; Schneider, Franziska; Watanabe, Hiroshi; Tsunoda, Satoshi P.; Vogt, Arend; Elstner, Marcus; Oertner, Thomas G.; Hegemann, Peter (2014-04-25). "Conversion of Channelrhodopsin into a Light-Gated Chloride Channel". Science. 344 (6182): 409–412. doi:10.1126/science.1249375. ISSN 0036-8075.
  2. Berndt, Andre; Lee, Soo Yeun; Ramakrishnan, Charu; Deisseroth, Karl (2014-04-25). "Structure-Guided Transformation of Channelrhodopsin into a Light-Activated Chloride Channel". Science. 344 (6182): 420–424. doi:10.1126/science.1252367. ISSN 0036-8075.
  3. Wietek, Jonas; Beltramo, Riccardo; Scanziani, Massimo; Hegemann, Peter; Oertner, Thomas G.; Wiegert, J. Simon (2015-10-07). "An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo". Scientific Reports. 5. doi:10.1038/srep14807. ISSN 2045-2322.
  4. Govorunova, Elena G.; Sineshchekov, Oleg A.; Janz, Roger; Liu, Xiaoqin; Spudich, John L. (2015-08-07). "Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics". Science. 349 (6248): 647–650. doi:10.1126/science.aaa7484. ISSN 0036-8075.
  5. Berndt, Andre; Lee, Soo Yeun; Wietek, Jonas; Ramakrishnan, Charu; Steinberg, Elizabeth E.; Rashid, Asim J.; Kim, Hoseok; Park, Sungmo; Santoro, Adam (2016-01-26). "Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity". Proceedings of the National Academy of Sciences. 113 (4): 822–829. doi:10.1073/pnas.1523341113. ISSN 0027-8424.
  6. Wietek, Jonas; Broser, Matthias; Krause, Benjamin S.; Hegemann, Peter (2016-02-19). "Identification of a Natural Green Light Absorbing Chloride Conducting Channelrhodopsin from Proteomonas sulcata". Journal of Biological Chemistry. 291 (8): 4121–4127. doi:10.1074/jbc.M115.699637. ISSN 0021-9258.
  7. Govorunova, Elena G.; Sineschekov, Oleg A.; Spudich, John L. (2016-02-01). "Proteomonas sulcata ACR1: A Fast Anion Channelrhodopsin". Photochemistry and Photobiology. 92 (2): 257–263. doi:10.1111/php.12558.
  8. Mahn, Mathias; Prigge, Matthias; Ron, Shiri; Levy, Rivka; Yizhar, Ofer. "Biophysical constraints of optogenetic inhibition at presynaptic terminals". Nature Neuroscience. 19 (4): 554–556. doi:10.1038/nn.4266.
  9. Evanko, Daniel. "Neuroscience: A better way to turn off neurons". Nature Methods. 11 (6): 608–608. doi:10.1038/nmeth.2988.
  10. Berndt, Andre; Deisseroth, Karl (2015-08-07). "Expanding the optogenetics toolkit". Science. 349 (6248): 590–591. doi:10.1126/science.aac7889. ISSN 0036-8075.
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