Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission

Han, Wenmin; Ma, Sui-Bin; Wu, Wenbin; Wang, Fu-Dong; Cao, Xinsheng; Wang, Dong-Hao; Wu, Haining; Xie, Rou‐Gang; Li, Zhenzhen; Wang, Fei; Wu, Shengxi; Zheng, Min; Luo, Ceng; Han, Hua

doi:10.1007/s12264-020-00617-0

Cited by 11 publications

(11 citation statements)

References 65 publications

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“…Another study found that the knockout of ttyh1 in mice via CRISPR-Cas9 led to a reduced pain response and reduced nociceptor excitability in mice. Knocking down ttyh1 in nociceptors resulted in reduced nociception and pain hypersensitivity in mice, further supporting the idea that ttyh1 plays a role in nociception (Han et al, 2021 ).…”

Section: Physiological Functions Of Tweety Proteinssupporting

confidence: 62%

“…Present in most invertebrates as a single gene or one with paralogs, the tweety genes encode chloride channels that are also highly conserved in most vertebrates where duplication events resulted in three distinct members, ttyh1–3 , each with unique expression patterns (Campbell et al, 2000 ; Suzuki and Mizuno, 2004 ; Matthews et al, 2007 ; Kumada et al, 2010 ). The role of chloride channels in general, and the tweety family in particular, have been implicated in a wide variety of cellular and physiological processes in the mature organism, including cell volume regulation, muscle and neuron excitability, neurite growth, nociception, immune cell activation, stem cell migration, and wound healing (Chen et al, 2010 ; Duran et al, 2010 ; Stefaniuk et al, 2010 ; Guo et al, 2016 ; Kim et al, 2018 ; Han et al, 2019 , 2021 ; Okada, 2019 ; Yasko et al, 2019 ). However, tweety genes are also prominently expressed throughout embryonic development, particularly in the nervous system, suggesting an important role in embryogenesis (Chen et al, 2010 ; Brown et al, 2015 ; Halleran et al, 2015 ; Poroca et al, 2017 ; Jentsch and Pusch, 2018 ; Karimi et al, 2018 ; Kim et al, 2018 ; Han et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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The tweety Gene Family: From Embryo to Disease

Nalamalapu

Yue

Stone

et al. 2021

Front. Mol. Neurosci.

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The tweety genes encode gated chloride channels that are found in animals, plants, and even simple eukaryotes, signifying their deep evolutionary origin. In vertebrates, the tweety gene family is highly conserved and consists of three members—ttyh1, ttyh2, and ttyh3—that are important for the regulation of cell volume. While research has elucidated potential physiological functions of ttyh1 in neural stem cell maintenance, proliferation, and filopodia formation during neural development, the roles of ttyh2 and ttyh3 are less characterized, though their expression patterns during embryonic and fetal development suggest potential roles in the development of a wide range of tissues including a role in the immune system in response to pathogen-associated molecules. Additionally, members of the tweety gene family have been implicated in various pathologies including cancers, particularly pediatric brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Here, we review the current state of research using information from published articles and open-source databases on the tweety gene family with regard to its structure, evolution, expression during development and adulthood, biochemical and cellular functions, and role in human disease. We also identify promising areas for further research to advance our understanding of this important, yet still understudied, family of genes.

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Section: Physiological Functions Of Tweety Proteinssupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

The tweety Gene Family: From Embryo to Disease

Nalamalapu

Yue

Stone

et al. 2021

Front. Mol. Neurosci.

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“…Further in vivo analysis by our research group showed that knockout of Ttyh1 leads to enhanced neurogenesis, suggesting that it may be an important regulator on quiescence/activation switch for NSCs ( Wu et al, 2019 ). In the mature neuron compartment, we have also shown that Ttyh1 participates pain perception ( Han et al, 2021 ). However, despite these findings, the precise role of Ttyh1 in NSCs in vivo and its specific biological mechanisms still await elucidation.…”

Section: Introductionmentioning

confidence: 89%

Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling

Cao

et al. 2021

Front. Cell Dev. Biol.

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The quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas the exact functions in vivo and precise mechanisms are still waiting to be elucidated. By constructing Ttyh1-promoter driven reporter mice, we determined the specific expression of Ttyh1 in quiescent NSCs and niche astrocytes. Further evaluations on Ttyh1 knockout mice revealed that Ttyh1 ablation leads to activated neurogenesis and enhanced spatial learning and memory in adult mice (6–8 weeks). Correspondingly, Ttyh1 deficiency results in accelerated exhaustion of NSC pool and impaired neurogenesis in aged mice (12 months). By RNA-sequencing, bioinformatics and molecular biological analysis, we found that Ttyh1 is involved in the regulation of calcium signaling in NSCs, and transcription factor NFATc3 is a critical effector in quiescence versus cell cycle entry regulated by Ttyh1. Our research uncovered new endogenous mechanisms that regulate quiescence versus activation of NSCs, therefore provide novel targets for the intervention to activate quiescent NSCs to participate in injury repair during pathology and aging.

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“…Highest differentially expressed G proteincoupled receptor mRNAs, ion channel mRNAs, circular RNAs, and long noncoding RNAs in the trigeminal ganglion after temporomandibular joint disorders G protein-coupled receptors, ion channels, circRNAs, and lncRNAs are critical in the modulation and transmission of nociceptive information (Zhao et al, 2013;Gottesman-Katz et al, 2021;Han et al, 2021;Yu et al, 2021;Zheng et al, 2021). 4A,B) and ion channel (Figures 4C,D) in the TG on CFA3D and CFA6D, respectively, after TMD are displayed in the heatmaps.…”

Section: Altered Expression Profiles Of Mrnas Circular Rnas and Long ...mentioning

confidence: 99%

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation

Liu

Zhao

Han

et al. 2022

Front. Cell Dev. Biol.

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Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund’s adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.

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Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission

Cited by 11 publications

References 65 publications

The tweety Gene Family: From Embryo to Disease

The tweety Gene Family: From Embryo to Disease

Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation

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