PUBLICATION

Optical control of metabotropic glutamate receptors

Authors
Levitz, J., Pantoja, C., Gaub, B., Janovjak, H., Reiner, A., Hoagland, A., Schoppik, D., Kane, B., Stawski, P., Schier, A.F., Trauner, D., and Isacoff, E.Y.
ID
ZDB-PUB-130322-5
Date
2013
Source
Nature Neuroscience   16(4): 507-16 (Journal)
Registered Authors
Isacoff, Ehud, Pantoja, Carlos, Schier, Alexander, Schoppik, David
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Escape Reaction/physiology
  • HEK293 Cells
  • Humans
  • Light*
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate/chemistry*
  • Receptors, Metabotropic Glutamate/physiology*
  • Synaptic Transmission/physiology
  • Zebrafish
PubMed
23455609 Full text @ Nat. Neurosci.
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.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping