Review
Cell Biology
Jeffrey L. Benovic
Summary: Agonist activation of G protein-coupled receptors leads to sequential interaction with G proteins, GRKs, and arrestins. GRKs play a central role in mediating the switch from G protein to arrestin interaction and controlling processes like receptor desensitization. Early studies on GRK identification and cloning laid the foundation for understanding the structure and function of these enzymes.
Article
Cell Biology
Ruxu Zhai, Jonathan Snyder, Sarah Montgomery, Priscila Y. Sato
Summary: This article reviews decades of research literature on the key roles of G-protein coupled receptor kinases (GRKs) and beta-arrestins in GPCR and non-GPCR cellular responses, as well as their involvement in various pathologies. The article concludes by highlighting the importance of future research in unraveling the novel roles of these proteins in metabolism and disease progression.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Marta Sanchez-Soto, Noelia M. Boldizsar, Kayla A. Schardien, Nora S. Madaras, Blair K. A. Willette, Laura R. Inbody, Christopher Dasaro, Amy E. Moritz, Julia Drube, Raphael S. Haider, R. Benjamin Free, Carsten Hoffman, David R. Sibley
Summary: The recruitment and activation of beta-arrestins to the D2 dopamine receptor (D2R) are not completely dependent on GPCR kinase (GRK)-mediated receptor phosphorylation, highlighting the importance of the GRK subfamily in D2R-beta-arrestin interactions.
Review
Cell Biology
Edda S. F. Matthees, Raphael S. Haider, Carsten Hoffmann, Julia Drube
Summary: This review discusses the regulatory mechanisms of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) and beta-arrestins, highlighting the importance of direct GPCR-GRK interactions and tissue-specific expression of GRKs and beta-arrestins in influencing GPCR phosphorylation patterns. The analysis of expression data for GRKs and beta-arrestins in different tissues provides insights into the pathophysiological dysregulation of the GPCR/GRK/beta-arrestin system, indicating the potential key role of tissue-specific perspectives in understanding the individual impact of different GRK isoforms on GPCR regulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Junaid Asghar, Liaque Latif, Stephen P. H. Alexander, David A. Kendall
Summary: The optimization protocol successfully increased sensitivity, reduced variance, and proved to be cost-effective for high-throughput screening of delta agonists. All DOPr agonists induced concentration-dependent ERK activation, which could be attenuated by pertussis toxin. Selective DOPr antagonists were able to antagonize the ERK activation induced by DOPr agonists.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vinay Kumar Sharma, Xuyu Yang, Soo-Kyung Kim, Amirhossein Mafi, Daniel Saiz-Sanchez, Patricia Villanueva-Anguita, Lan Xiao, Asuka Inoue, William A. Goddard, Y. Peng Loh
Summary: Interaction between NF-alpha 1/CPE and 5-HTR1E activates the beta-arrestin/ERK/CREB/BCL2 pathway to protect neurons from oxidative stress and neuroexcitotoxicity, preventing cognitive dysfunction.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yixin Zhang, Peilan Zhou, Fengfeng Lu, Ruibin Su, Zehui Gong
Summary: Overexpression of A20-binding inhibitor of nuclear factor-kappa B (ABIN-1) attenuated morphine tolerance and dependence in mice, likely through facilitating beta-arrestin2 degradation. ABIN-1 targeted beta-arrestin2 to regulate morphine tolerance, suggesting it as a potential therapeutic target for alleviating morphine tolerance and dependence.
MOLECULAR PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Leonard Girnita, Terry J. Smith, Joseph A. M. J. L. Janssen
Summary: This article reviews the generation of autoantibodies in thyroid eye disease (TED) and their direct effects on orbital fibroblast responses through the TSH receptor (TSHR), IGF-I receptor (IGF-IR), or both. Evidence suggests that IGF-IR functions not only as a typical tyrosine kinase receptor, but also as a functional receptor tyrosine kinase/G-protein-coupled receptor hybrid. Teprotumumab, a monoclonal IGF-IR antibody, effectively reduces TED disease activity and its in vitro actions on fibrocytes and orbital fibroblasts. The article proposes four possible IGF-IR activation models underlying the clinical responses to teprotumumab in TED patients.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Cell Biology
Bari Aamna, Aritra Kumar Dan, Raghaba Sahu, Santosh Kumar Behera, Sagarika Parida
Summary: beta-Arrestins are intracellular proteins with various functions, playing roles in GPCR desensitization, receptor endocytosis, and ubiquitylation. They also act as adaptor proteins, controlling the recruitment, activation, and scaffolding of signaling complexes, and participate in cellular processes such as proliferation, migration, apoptosis, and transcription. Additionally, their involvement in cancer onset and progression has been recognized.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Riko Tatsumi, Saki Aihara, Seiya Matsune, Junken Aoki, Asuka Inoue, Takao Shimizu, Motonao Nakamura
Summary: This study reveals the role of phosphorylation in signal transduction of G protein-coupled receptor BLT1. The results show that different concentrations of LTB4 can induce phosphorylation of BLT1 on Ser(310) and Thr(308), thus regulating its binding with beta-arrestin and altering signal transduction.
Article
Physiology
Abigail Pearce, Theo Redfern-Nichols, Matthew Harris, David R. Poyner, Mark Wigglesworth, Graham Ladds
Summary: This study focused on the desensitisation of CLR-RAMP complexes in response to peptide agonists, finding different RAMP subunits have varying effects on beta-arrestin recruitment and internalisation, and that internalisation of CLR depends on beta-arrestin but is not required for full agonism. Overexpression of GRKs decreases receptor signalling by reducing surface expression of the CLR-RAMP complex. These findings provide a systematic analysis of the role of beta-arrestins and GRKs in CLR-RAMP signal transduction and open the door to further investigation into other Class B1 GPCRs.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emily Dean, Vikash Kumar, Ashleigh McConnell, Iohana B. Pagnoncelli, Chun Wu
Summary: This study investigated the activation mechanism of the delta-opioid receptor (DOR), identified key residues involved in the activation pathway, and provided essential information for experimental mutagenesis studies, facilitating the development of therapeutic agents targeting DOR.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Anesthesiology
Akane Komatsu, Kanako Miyano, Daisuke Nakayama, Yusuke Mizobuchi, Eiko Uezono, Kaori Ohshima, Yusuke Karasawa, Yui Kuroda, Miki Nonaka, Keisuke Yamaguchi, Masako Iseki, Yasuhito Uezono, Masakazu Hayashida
Summary: The compounds N1 and N2 have high transdermal absorbability and equivalent analgesic effects as morphine. They may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.
ANESTHESIA AND ANALGESIA
(2022)
Article
Cell Biology
Nour Zaimia, Joelle Obeid, Annie Varrault, Julia Sabatier, Christophe Broca, Patrick Gilon, Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
Summary: Glucagon-like peptide 1 (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIPR) receptors play important roles in glucose homeostasis. This study highlights the distinct roles of ARRB2 in regulating GLP-1R and GIPR signaling, as well as the potential consequences of its decreased expression in pathological conditions such as diabetes.
Article
Biochemistry & Molecular Biology
Elodie Blondel-Tepaz, Marie Leverve, Badr Sokrat, Justine S. Paradis, Milena Kosic, Kusumika Saha, Cedric Auffray, Evelyne Lima-Fernandes, Alessia Zamborlini, Anne Poupon, Louis Gaboury, Jane Findlay, George S. Baillie, Herve Enslen, Michel Bouvier, Stephane Angers, Stefano Marullo, Mark G. H. Scott
Summary: The protein beta-arrestin2 plays a critical role in regulating the Mdm2-p53 signaling axis by promoting the nuclear-cytoplasmic shuttling of Mdm2 and enhancing p53 signaling. While beta-arrestin2 can be SUMOylated, it is the non-covalent interaction between SUMO and beta-arrestin2, mediated by a SUMO interaction motif (SIM), that is essential for its cytonuclear trafficking function. Depletion of the RanBP2/RanGAP1-SUMO nucleocytoplasmic transport hub leads to defective beta-arrestin2 nuclear entry, inhibiting its ability to displace Mdm2 from the nucleus and enhancing p53 signaling in cancer cells.
Article
Biochemistry & Molecular Biology
Changyou Jiang, Xueying Wang, Qiumin Le, Peipei Liu, Cao Liu, Zhilin Wang, Guanhong He, Ping Zheng, Feifei Wang, Lan Ma
Summary: The study reveals that morphine coordinates the function of SST- and PV-INs in the PrL via different opioid receptors to disinhibit pyramidal neurons and enhance reward.
MOLECULAR PSYCHIATRY
(2021)
Article
Cell & Tissue Engineering
Man Xiong, Yezheng Tao, Qinqin Gao, Ban Feng, Wei Yan, Yingying Zhou, Thomas A. Kotsonis, Tingli Yuan, Zhiwen You, Ziyan Wu, Jiajie Xi, Alexander Haberman, Julia Graham, Jasper Block, Wenhao Zhou, Yuejun Chen, Su-Chun Zhang
Summary: The study demonstrates that human embryonic stem cell-derived neurons have the ability to repair specific circuits and restore functionality in the adult brain, leading to improvements in motor function.
Article
Biochemistry & Molecular Biology
Xin Dong, Shi-Bo Xu, Xin Chen, Mengdan Tao, Xiao-Yan Tang, Kai-Heng Fang, Min Xu, Yufeng Pan, Yuejun Chen, Shuijin He, Yan Liu
Summary: The study demonstrated the successful transplantation of human cerebral organoids into the mouse brain cortex, with the organoids surviving and extending neural projections over 4.5 mm in length within 1 month. The transplanted organoids generated mature neurons and formed synaptic connections with host neurons, integrating into existing neural circuits and impacting the neural behavior of the mice.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Wenxiang Fan, Ying Zhang, Xiaomin Li, Chi Xu
Summary: This study confirmed the protective effect of S-ORC on cognitive recovery after MCAO/R in rats, and identified alpha 7nAChR and PI3K as key molecules mediating the cognitive restoration induced by S-ORC.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yunlong Tao, Scott C. Vermilyea, Matthew Zammit, Jianfeng Lu, Miles Olsen, Jeanette M. Metzger, Lin Yao, Yuejun Chen, Sean Phillips, James E. Holden, Viktoriya Bondarenko, Walter F. Block, Todd E. Barnhart, Nancy Schultz-Darken, Kevin Brunner, Heather Simmons, Bradley T. Christian, Marina E. Emborg, Su-Chun Zhang
Summary: The degeneration of dopamine neurons in the midbrain is the underlying cause of Parkinson's disease. While fetal mesencephalic tissue transplantation can improve motor symptoms, the outcomes vary due to undefined and unstandardized donor tissues. Induced pluripotent stem cells offer a potential autologous transplantation therapy for PD, but its efficacy remains uncertain, especially in primates.
Article
Biochemistry & Molecular Biology
Changyou Jiang, Xiao Yang, Guanhong He, Fan Wang, Zhilin Wang, Wendong Xu, Ying Mao, Lan Ma, Feifei Wang
Summary: Neuronal plasticity in the ventral tegmental area (VTA) is crucial for drug dependence, with morphine exposure leading to preferential projection of neurons to the nucleus accumbens (NAc) and dopamine-dependent positive reinforcement. Chronic morphine exposure enhances connections between corticotrophin-releasing hormone (CRH) neurons of the central amygdala and VTA neurons, mediating negative effects during opiate withdrawal. Pharmacological intervention or CRISPR-mediated repression of CRH receptors weakens inhibitory inputs and alleviates negative effects during opiate withdrawal.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Ying Zhang, Chi Xu
Summary: This review introduces the synthesis and secretion mechanism of exosomes, discusses their relationship with hippocampal neurogenesis, mood and cognition, and psychiatric disorders. It also explores their roles in regulating depression, epilepsy, and schizophrenia, as well as their prospects in diagnosing CNS disorders.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Clinical Neurology
Xiaoli Ji, Yingying Zhou, Qinqin Gao, Hui He, Ziyan Wu, Ban Feng, Yuting Mei, Yan Cheng, Wenhao Zhou, Yuejun Chen, Man Xiong
Summary: This study demonstrates that transplanted neural progenitors derived from human embryonic stem cells can repair damaged neural circuits and rescue developmental and motor defects in the brains of mice with hypoxic-ischaemic encephalopathy.
Article
Biochemistry & Molecular Biology
Chi Xu, Yun Cheng, Manman Han, Yimin Tao, Jing-Gen Liu
Summary: Our study found that activation of adenosine A1 receptor inhibits the MAPK signaling pathway mediated by delta opioid receptor through heterologous desensitization of the Raf-1/MEK/ERK cascade.
NEUROCHEMICAL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Yunyun Li, Xiaodie Liu, Qianqian Fu, Wenxiang Fan, Xiaomei Shao, Jianqiao Fang, Jing-Gen Liu, Chi Xu
Summary: This study investigates the mechanism underlying the effective complementary therapy, electroacupuncture, in treating chronic pain comorbid depression. It is found that the therapy has a persistent effect and restores Tet1 expression, preventing hypermethylation of the Prox1 gene and supporting normal neurogenesis. This study provides a novel idea for the treatment of chronic pain-induced depression.
Article
Cell & Tissue Engineering
Zhiwen You, Luyue Wang, Hui He, Ziyan Wu, Xinyue Zhang, Shuaixiang Xue, Peibo Xu, Yanhong Hong, Man Xiong, Wu Wei, Yuejun Chen
Summary: Single-cell split barcoding (SISBAR) allows clonal tracking of single-cell transcriptomes across stages, revealing a multi-level clonal lineage landscape. The study shows that transcriptome-defined cell types can arise from distinct lineages, each with distinct molecular signatures.
Article
Biochemical Research Methods
Lianshun Xie, Hengxin Liu, Zhiwen You, Luyue Wang, Yiwen Li, Xinyue Zhang, Xiaoshan Ji, Hui He, Tingli Yuan, Wenping Zheng, Ziyan Wu, Man Xiong, Wu Wei, Yuejun Chen
Summary: A fundamental interest in developmental neuroscience is mapping single-cell lineages in the brain. Researchers developed a CRISPR editing-based lineage-specific tracing method called CREST and used it to map single-cell lineages in the developing mouse ventral midbrain (vMB). They identified different progenitor types and clonal lineages using the CREST method and associated progenitor cell transcriptomes with their differentiation potentials using pandaCREST. This comprehensive single-cell lineage analysis provides new insights into neural specification and offers a dual-recorder single-cell lineage tracing method for the mouse brain called CREST.
Article
Medicine, Research & Experimental
Peibo Xu, Hui He, Qinqin Gao, Yingying Zhou, Ziyan Wu, Xiao Zhang, Linyu Sun, Gang Hu, Qian Guan, Zhiwen You, Xinyue Zhang, Wenping Zheng, Man Xiong, Yuejun Chen
Summary: This study provides insights into the cellular heterogeneity during midbrain dopaminergic (mDA) neuron differentiation and establishes a strategy to generate highly purified donor cells for stable and predictable therapeutic outcomes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell & Tissue Engineering
Chi Xu, Wenxiang Fan, Ying Zhang, Horace H. Loh, Ping-Yee Law
Summary: This study reveals that OPRK1 agonists inhibit adult neurogenesis in the mouse hippocampus by upregulating the expression of miR-7a, which in turn downregulates Pax6/Neurog2/NeuroD1 activities and hinders neuronal differentiation of neural stem cells.
Article
Multidisciplinary Sciences
Yi Dong, Man Xiong, Yuejun Chen, Yezheng Tao, Xiang Li, Anita Bhattacharyya, Su-Chun Zhang