Review
Cell Biology
Mariacristina Mazzitelli, Peyton Presto, Nico Antenucci, Shakira Meltan, Volker Neugebauer
Summary: Metabotropic glutamate receptors (mGluR) are important in the nervous system and have implications in various pathological conditions including pain. Pharmacological manipulation of mGluR subtypes may be a promising approach for the treatment of pain and other disorders.
Article
Neurosciences
Ruth C. Werthmann, Manuel Tzouros, Jens Lamerz, Angelique Augustin, Thorsten Fritzius, Luca Trovo, Michal Stawarski, Adi Raveh, Catherine Diener, Christophe Fischer, Martin Gassmann, Lothar Lindemann, Bernhard Bettler
Summary: Recent studies have shown that mGlu1 and mGlu5 form functional heterodimers in the brain, exhibiting symmetric signal transduction where both protomers need to reach an active conformation for full receptor activity. This highlights differences in the signaling transduction of heterodimeric mGluRs that influence allosteric modulation.
Article
Biology
Alexander S. Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E. Gloriam
Summary: Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors coupled to G proteins, but there are differences in the reported G protein couplings among recent large-scale datasets. This study presents a common coupling map that uncovers novel couplings, GPCR-G protein selectivity, and the comparison of co-coupling and co-expression of G proteins with phylogenetic relationships. These findings will advance receptor research and cellular signaling, and contribute to the development of safer drugs.
Review
Medicine, Research & Experimental
Nadia Rabeh, Baraa Hajjar, Jude O. Maraka, Ashwin F. Sammanasunathan, Mohammed Khan, Saif M. I. Alkhaaldi, Samy Mansour, Rashed T. Almheiri, Hamdan Hamdan, Khaled S. Abd-Elrahman
Summary: This review discusses the research on targeting glutamate receptors for the treatment of neurodegenerative diseases. By activating group III mGluRs, the release of glutamate can be inhibited, offering potential therapeutic options. Despite the availability of pharmacological ligands, their use in neurodegenerative diseases is limited, except for Parkinson's disease, and further research is needed.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medicine, Research & Experimental
Nadia Rabeh, Baraa Hajjar, Jude O. Maraka, Ashwin F. Sammanasunathan, Mohammed Khan, Saif M. I. Alkhaaldi, Samy Mansour, Rashed T. Almheiri, Hamdan Hamdan, Khaled S. Abd-Elrahman
Summary: This article discusses the importance of glutamate receptors in the treatment of neurodegenerative diseases and the potential of developing new drugs targeting these receptors.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Vanessa Pereira, Juri Aparicio Arias, Amadeu Llebaria, Cyril Goudet
Summary: Neuropathic pain is a challenging condition to manage. In this study, the role of the amygdala in regulating neuropathic pain was investigated. The activation of mGlu4 receptors in the amygdala was found to alleviate sensory and depressive-like symptoms in a mouse model of neuropathy.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Etienne de Coulon, Christian Dellenbach, Stephan Rohr
Summary: The LSSE system allows for comprehensive intracellular electrical recordings on cells undergoing strain events, providing stable conditions for studying mechanically activated ion currents. This system offers advanced insights into mechanosensitive ion channel function and allows for quantitative comparisons among different types of channels and cells.
Article
Chemistry, Multidisciplinary
Akinobu Senoo, Yutaro Yamada, Kento Ojima, Tomohiro Doura, Itaru Hamachi, Shigeki Kiyonaka
Summary: Cell-surface receptors play a crucial role in transducing extracellular signals, and their physiological functions depend on the cell type. In this study, we developed an orthogonal activation method for the metabotropic glutamate receptor 1 (mGlu1) using coordination-based chemogenetics. Through protein design and screening, we identified mGlu1 mutants that could be directly activated by coordination with specific metal ions, providing cell-type selectivity.
FRONTIERS IN CHEMISTRY
(2022)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Yong Liu, You Wang, Juan Yang, Tao Xu, Changhong Tan, Peng Zhang, Qiankun Liu, Yangmei Chen
Summary: The study identified that GIPC1 is downregulated in patients with epilepsy and mice with induced epilepsy, and it interacts with mGluR7 to regulate epileptogenesis by increasing mGluR7 expression.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Irene Martinez-Gallego, Antonio Rodriguez-Moreno, Yuniesky Andrade-Talavera
Summary: In this article, the involvement of group I mGluRs in STDP and their possible role as coincidence detectors are briefly reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Nohely Abreu, Amanda Acosta-Ruiz, Guoqing Xiang, Joshua Levitz
Summary: This study investigates the distinct regulation of different subtypes of mGluR family using fluorescence imaging and electrophysiology. The research reveals significant differences in rapid desensitization and internalization between subtypes, with a focus on the properties of mGluR3 and its interaction with GPCR kinases and beta-arrestins. The identification of a cancer-associated mutation within mGluR3 highlights the potential for biased variants and provides insight into the functional roles of mGluR subtypes.
Article
Neurosciences
Wenqi Fu, Luca Franchini, Cesare Orlandi
Summary: This study generated new GPRC5B polyclonal antibodies and investigated the expression levels of GPRC5B in different organs and brain regions. It was found that GPRC5B had high levels of glycosylation in the mouse brain and was expressed at the highest level in the olfactory bulb, hippocampus, cerebellum, and pons. GABAergic neurons showed higher expression levels of Gprc5b than glutamatergic neurons in most regions.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Cell Biology
Preeti Kumari Chaudhary, Soochong Kim
Summary: GPCRs play a crucial role in cancer progression, but the specific mechanisms of their involvement are still unclear. Studies have revealed the multifaceted impact of GPCRs on cancer development and the signaling pathways involved.
Article
Biochemistry & Molecular Biology
Dilip Rai, Takumi Akagi, Atsushi Shimohata, Toshiyuki Ishii, Mie Gangi, Takuma Maruyama, Yuko Wada-Kiyama, Ikuo Ogiwara, Makoto Kaneda
Summary: The intracellular C-terminal domain of mGluR6 is essential for its cell surface localization and receptor function, with specific amino acid deletions affecting these processes. The CTD may also contain regulatory elements for intracellular trafficking and signaling, as indicated by conservation of amino acids resembling an ER retention motif.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Chemistry, Medicinal
Junfeng Wang, Xiying Qu, Timothy M. Shoup, Gengyang Yuan, Sepideh Afshar, Chuzhi Pan, Aijun Zhu, Ji-Kyung Choi, Hye Jin Kang, Pekka Poutiainen, Georges El Fakhri, Zhaoda Zhang, Anna-Liisa Brownell
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Reed M. Stein, Hye Jin Kang, John D. McCorvy, Grant C. Glatfelter, Anthony J. Jones, Tao Che, Samuel Slocum, Xi-Ping Huang, Olena Savych, Yurii S. Moroz, Benjamin Stauch, Linda C. Johansson, Vadim Cherezov, Terry Kenakin, John J. Irwin, Brian K. Shoichet, Bryan L. Roth, Margarita L. Dubocovich
Review
Cell Biology
Theodore G. Wensel
Article
Chemistry, Medicinal
Gengyang Yuan, Xiying Qu, Baohui Zheng, Ramesh Neelamegam, Sepideh Afshar, Suhasini Iyengar, Chuzhi Pan, Junfeng Wang, Hye Jin Kang, Mary Jo Ondrechen, Pekka Poutiainen, Georges El Fakhri, Zhaoda Zhang, Anna-Liisa Brownell
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Gengyang Yuan, Nicolas J. Guehl, Baohui Zheng, Xiying Qu, Sung-Hyun Moon, Maeva Dhaynaut, Timothy M. Shoup, Sepideh Afshar, Hye Jin Kang, Zhaoda Zhang, Georges El Fakhri, Marc D. Normandin, Anna-Liisa Brownell
Summary: The study synthesized the first F-18-labeled mGluR2 imaging ligand [F-18]8, showing good reversible binding characteristics and metabolic stability in rodents and non-human primates. Pre-treatment studies revealed that compound 7 can affect the accumulation of [F-18]8 in mGluR2-rich regions.
MOLECULAR IMAGING AND BIOLOGY
(2021)
Article
Chemistry, Medicinal
Edem K. Onyameh, Edward Ofori, Barbara A. Bricker, Uma M. Gonela, Suresh V. K. Eyunni, Hye J. Kang, Chandrashekar Voshavar, Seth Y. Ablordeppey
Summary: Compound 1c, previously known for its high affinity binding to the 5-HT7 receptor, was found to racemize easily during enantiomeric separation. To prevent this, methyl and carboxyethyl analogs, compounds 2 and 3, were synthesized and showed similar binding affinities. Enantiomeric separation revealed that the levorotatory enantiomer 2a had higher affinity and a beta-arrestin biased functional selectivity for the 5-HT7 receptor compared to the dextrorotatory enantiomer 2b.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Neurosciences
Kerri D. Pryce, Hye Jin Kang, Farhana Sakloth, Yongfeng Liu, Susan Khan, Katalin Toth, Abhijeet Kapoor, Andrew Nicolais, Tao Che, Lihuai Qin, Feodora Bertherat, H. Umit Kaniskan, Jian Jin, Michael D. Cameron, Bryan L. Roth, Venetia Zachariou, Marta Filizola
Summary: The study found that two MOR PAMs molecules can maximize the analgesic effects of opioid drugs while reducing adverse reactions and overdose risks. These molecules show efficacy in mouse pain models and do not enhance adverse reactions associated with opioid drugs.
Review
Physiology
Theodore G. Wensel, Valencia L. Potter, Abigail Moye, Zhixian Zhang, Michael A. Robichaux
Summary: The rod and cone photoreceptor cells of the vertebrate retina have specialized structures that enable them to carry out light detection over a broad range of illumination intensities. These structures support their daily function and phototransduction through specialized organization.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Valencia L. Potter, Abigail R. Moye, Michael A. Robichaux, Theodore G. Wensel
Summary: Mutations in the CEP290 gene cause retinal degeneration. Studies using microscopy revealed the precise localization and functional roles of CEP290, indicating its crucial role in the connecting cilia of photoreceptors.
Article
Biochemistry & Molecular Biology
Melina A. Agosto, Abiodun Adefola R. Adeosun, Nitin Kumar, Theodore G. Wensel
Summary: This study investigates the role of mGluR6 in synaptic localization and function in the retinal photoreceptor signal transduction pathway. It was found that multiple regions in the ligand-binding domain of mGluR6 are necessary for synaptic localization and ELFN1 binding. The study proposes a model in which trans-synaptic ELFN1 binding is required for mGluR6 postsynaptic localization, while the C-terminus plays a role in mGluR6 in ON-BCs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Gengyang Yuan, Maeva Dhaynaut, Yu Lan, Nicolas J. Guehl, Dalena Huynh, Suhasini M. Iyengar, Sepideh Afshar, Manish Kumar Jain, Julie E. Pickett, Hye Jin Kang, Hao Wang, Sung-Hyun Moon, Mary Jo Ondrechen, Changning Wang, Timothy M. Shoup, Georges El Fakhri, Marc D. Normandin, Anna-Liisa Brownell
Summary: Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders, and [C-11]13 shows potential as a PET imaging probe for studying mGluR2 function.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Eunna Huh, Jonathan Gallion, Melina A. Agosto, Sara J. Wright, Theodore G. Wensel, Olivier Lichtarge
Summary: The study suggests that somatic mutations across class A GPCRs are nonrandomly distributed, with impactful, recurrent mutations at selected positions of functional motifs. These mutations induce perturbation of G protein activation and/or beta-arrestin recruitment in multiple receptors, promoting tumor growth or survival. The findings open a window into cancer mechanisms and potential therapeutic approaches by revealing that multiple GPCRs can drive or enable cancer through mutations at cognate positions across GPCR paralogs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Michael A. Robichaux, Vy Nguyen, Fung Chan, Lavanya Kailasam, Feng He, John H. Wilson, Theodore G. Wensel
Summary: The P23H-Rho-RFP mouse model provides a useful tool for studying the pathology and treatment of P23H-Rho and adRP. Mutant rod cells undergo an adaptive process that prolongs survival despite unfolded protein accumulation in the endoplasmic reticulum.
DISEASE MODELS & MECHANISMS
(2022)
Article
Multidisciplinary Sciences
Can Cao, Hye Jin Kang, Isha Singh, He Chen, Chengwei Zhang, Wenlei Ye, Byron W. Hayes, Jing Liu, Ryan H. Gumpper, Brian J. Bender, Samuel T. Slocum, Brian E. Krumm, Katherine Lansu, John D. McCorvy, Wesley K. Kroeze, Justin G. English, Jeffrey F. DiBerto, Reid H. J. Olsen, Xi-Ping Huang, Shicheng Zhang, Yongfeng Liu, Kuglae Kim, Joel Karpiak, Lily Y. Jan, Soman N. Abraham, Jian Jin, Brian K. Shoichet, Jonathan F. Fay, Bryan L. Roth
Summary: Structural studies of MRGPRX2 and MRGPRX4 in complex with endogenous and synthetic ligands provide insights for developing therapeutic compounds for pain, itch, and mast cell-mediated hypersensitivity. These receptors are key mediators of itch and related mast cell-mediated hypersensitivity reactions.
Article
Biology
Ammaji Rajala, Feng He, Robert E. Anderson, Theodore G. Wensel, Raju V. S. Rajala