Optical Control of Metabotropic Glutamate Receptors
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Author
Levitz, Joshua
Pantoja, Carlos
Gaub, Benjamin
Janovjak, Harald
Reiner, Andreas
Hoagland, Adam
Kane, Brian
Stawski, Philipp
Trauner, Dirk
Isacoff, Ehud Y.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nn.3346Metadata
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Levitz, J., C. Pantoja, B. Gaub, H. Janovjak, A. Reiner, A. Hoagland, D. Schoppik, et al. 2013. “Optical Control of Metabotropic Glutamate Receptors.” Nature neuroscience 16 (4): 507-516. doi:10.1038/nn.3346. http://dx.doi.org/10.1038/nn.3346.Abstract
G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681425/pdf/Terms of Use
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