title: Optical control of metabotropic glutamate receptors.
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.
authors: Biophysics Graduate Group, University of California, Berkeley, California, USA.
authors: Joshua
authors: J
authors: Levitz
authors: Carlos
authors: C
authors: Pantoja
authors: Benjamin
authors: B
authors: Gaub
authors: Harald
authors: H
authors: Janovjak
authors: Andreas
authors: A
authors: Reiner
authors: Adam
authors: A
authors: Hoagland
authors: David
authors: D
authors: Schoppik
authors: Brian
authors: B
authors: Kane
authors: Philipp
authors: P
authors: Stawski
authors: Alexander F
authors: AF
authors: Schier
authors: Dirk
authors: D
authors: Trauner
authors: Ehud Y
authors: EY
authors: Isacoff
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004924:Escape Reaction / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D055620:Optical Phenomena; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D015027:Zebrafish
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2