Volume 32, No 7, Jul 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 7, July 2022: 695-698   |  Open Access

LETTERS TO THE EDITOR

Structural basis of the activation of metabotropic glutamate receptor 3

Wei Fang^1,† , Fan Yang^1,† , Chanjuan Xu^2,3,† , Shenglong Ling^1,† , Li Lin² , Yingxin Zhou¹ , Wenjing Sun¹ , Xiaomei Wang² , Peng Liu² , Philippe Rondard⁴ , Pan Shi^1,* , Jean-Philippe Pin^4,* , Changlin Tian^1,* , Jianfeng Liu^2,3,*

¹The First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, Joint Center for Biological Analytical Chemistry, Anhui Engineering Laboratory of Peptide Drug, Anhui Laboratory of Advanced Photonic Science and Technology, University of Science and Technology of China, Hefei, Anhui, China
²Key Laboratory of Molecular Biophysics of MOE, International Research Center for Sensory Biology and Technology of MOST, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China
³Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
⁴Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, Montpellier, France
^†These authors contributed equally: Wei Fang, Fan Yang, Chanjuan Xu, Shenglong Ling
Correspondence: Pan Shi(shipan@ustc.edu.cn)Jean-Philippe Pin(jean-philippe.pin@igf.cnrs.fr)Changlin Tian(cltian@ustc.edu.cn)Jianfeng Liu(jfliu@mail.hust.edu.cn)

Dear Editor,

Glutamate is used by most synapses in the brain and responsible for fast excitatory transmission, thus playing important roles in excitotoxicity and ammonium detoxification in the brain.1 Eight G protein-coupled metabotropic glutamate receptors (mGlus) are essential in sensing glutamate concentrations from the ten nanomolar to ten millimolar range in the brain.2 The mGlu3 is in high sequence homology with mGlu2, but mGlu3 is of greater interest because it is responsible for the detection of very low concentrations of glutamate.2 The mGlu3 is found in astrocytes and in both pre- and post-synaptic elements in neurons, whereas mGlu2 is mainly distributed in neurons, particularly in the preterminal region of axons, far from the active zone of neurotransmitter release.3 Accumulating evidence supports a role of mGlu3 not only in maintaining synaptic homeostasis but also in promoting neuronal and astrocyte survival in several pathological conditions.4 The mGlu3 has garnered attention as a potent therapeutic target for both psychiatric disorders and neurodegenerative diseases such as schizophrenia, Alzheimer’s disease, anxiety, depression, pain and addiction.5,6 Polymorphic variants of the gene encoding mGlu3 are linked to schizophrenia. Furthermore, recent studies have suggested that negative allosteric modulators (NAMs) of both mGlu3 and mGlu2 induced rapid antidepressant-like effects through related but divergent mechanisms of action.7 Moreover, the high sequence homology of mGlu3 and mGlu2 restricts the development of selective ligands, which demands the structures of mGlu3.

https://doi.org/10.1038/s41422-022-00623-z

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