Optical control of metabotropic glutamate receptors

Joshua Levitz, Carlos Pantoja, Benjamin Gaub, Harald Janovjak, Andreas Reiner, Adam Hoagland, David Schoppik, Brian Kane, Philipp Stawski, Alexander F. Schier, Dirk Trauner, Ehud Y. Isacoff

Research output: Contribution to journalArticle

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 of native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized mGluRs (LimGluRs). The light-agonized LimGluR2, on which we focused, was fast, bistable and supported multiple rounds of on/off switching. Light gated two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. We found that the light-antagonized tool LimGluR2-block was able to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalized the optical control to two additional family members: mGluR3 and mGluR6. This system worked in rodent brain slices and in zebrafish in vivo, where we found that mGluR2 modulated the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.

Original languageEnglish (US)
Pages (from-to)507-516
Number of pages10
JournalNature Neuroscience
Volume16
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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    Levitz, J., Pantoja, C., Gaub, B., Janovjak, H., Reiner, A., Hoagland, A., Schoppik, D., Kane, B., Stawski, P., Schier, A. F., Trauner, D., & Isacoff, E. Y. (2013). Optical control of metabotropic glutamate receptors. Nature Neuroscience, 16(4), 507-516. https://doi.org/10.1038/nn.3346