Pub Date : 2024-07-16DOI: 10.1126/scisignal.add8913
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefanie Raps, Friederike Hecker, Matthias Pierer, Erik Schilling, Elke Lainka, Tilmann Kallinich, Sven Baumann, Katarina Fritz-Wallace, Ulrike Rolle-Kampczyk, Martin von Bergen, Achim Aigner, Alexander Ewe, Georg Schett, Michael Cross, Manuela Rossol, Ulf Wagner
Hypoxia and low glucose abundance often occur simultaneously at sites of inflammation. In monocytes and macrophages, glucose-oxygen deprivation stimulates the assembly of the NLRP3 inflammasome to generate the proinflammatory cytokine IL-1β. We found that concomitant glucose deprivation and hypoxia activated the NLRP3 inflammasome by constraining the function of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate kinase pathway. HMGCR is involved in the synthesis of geranylgeranyl pyrophosphate (GGPP), which is required for the prenylation and lipid membrane integration of proteins. Under glucose-oxygen deprivation, GGPP synthesis was decreased, leading to reduced prenylation of the small GTPase Rac1, increased binding of nonprenylated Rac1 to the scaffolding protein IQGAP1, and enhanced activation of the NLRP3 inflammasome. In response to restricted oxygen and glucose supply, patient monocytes with a compromised mevalonate pathway due to mevalonate kinase deficiency or Muckle-Wells syndrome released more IL-1β than did control monocytes. Thus, reduced GGPP synthesis due to inhibition of HMGCR under glucose-oxygen deprivation results in proinflammatory innate responses, which are normally kept in check by the prenylation of Rac1. We suggest that this mechanism is also active in inflammatory autoimmune conditions.
{"title":"Glucose-oxygen deprivation constrains HMGCR function and Rac1 prenylation and activates the NLRP3 inflammasome in human monocytes","authors":"Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefanie Raps, Friederike Hecker, Matthias Pierer, Erik Schilling, Elke Lainka, Tilmann Kallinich, Sven Baumann, Katarina Fritz-Wallace, Ulrike Rolle-Kampczyk, Martin von Bergen, Achim Aigner, Alexander Ewe, Georg Schett, Michael Cross, Manuela Rossol, Ulf Wagner","doi":"10.1126/scisignal.add8913","DOIUrl":"10.1126/scisignal.add8913","url":null,"abstract":"<div >Hypoxia and low glucose abundance often occur simultaneously at sites of inflammation. In monocytes and macrophages, glucose-oxygen deprivation stimulates the assembly of the NLRP3 inflammasome to generate the proinflammatory cytokine IL-1β. We found that concomitant glucose deprivation and hypoxia activated the NLRP3 inflammasome by constraining the function of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate kinase pathway. HMGCR is involved in the synthesis of geranylgeranyl pyrophosphate (GGPP), which is required for the prenylation and lipid membrane integration of proteins. Under glucose-oxygen deprivation, GGPP synthesis was decreased, leading to reduced prenylation of the small GTPase Rac1, increased binding of nonprenylated Rac1 to the scaffolding protein IQGAP1, and enhanced activation of the NLRP3 inflammasome. In response to restricted oxygen and glucose supply, patient monocytes with a compromised mevalonate pathway due to mevalonate kinase deficiency or Muckle-Wells syndrome released more IL-1β than did control monocytes. Thus, reduced GGPP synthesis due to inhibition of HMGCR under glucose-oxygen deprivation results in proinflammatory innate responses, which are normally kept in check by the prenylation of Rac1. We suggest that this mechanism is also active in inflammatory autoimmune conditions.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 845","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1126/scisignal.adg4124
Holli Carden, Katherine L. Harper, Timothy J. Mottram, Oliver Manners, Katie L. Allott, Mark L. Dallas, David J. Hughes, Jonathan D. Lippiat, Jamel Mankouri, Adrian Whitehouse
Kaposi’s sarcoma–associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi’s sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K+ channel Kv1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of Kv1.3 and led to enhanced K+ channel activity and hyperpolarization of the B cell membrane. Enhanced Kv1.3 activity promoted intracellular Ca2+ influx, leading to the Ca2+-driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by Kv1.3 blockers or silencing. These findings highlight Kv1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication.
{"title":"Kv1.3-induced hyperpolarization is required for efficient Kaposi’s sarcoma–associated herpesvirus lytic replication","authors":"Holli Carden, Katherine L. Harper, Timothy J. Mottram, Oliver Manners, Katie L. Allott, Mark L. Dallas, David J. Hughes, Jonathan D. Lippiat, Jamel Mankouri, Adrian Whitehouse","doi":"10.1126/scisignal.adg4124","DOIUrl":"10.1126/scisignal.adg4124","url":null,"abstract":"<div >Kaposi’s sarcoma–associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi’s sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K<sup>+</sup> channel K<sub>v</sub>1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of K<sub>v</sub>1.3 and led to enhanced K<sup>+</sup> channel activity and hyperpolarization of the B cell membrane. Enhanced K<sub>v</sub>1.3 activity promoted intracellular Ca<sup>2+</sup> influx, leading to the Ca<sup>2+</sup>-driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by K<sub>v</sub>1.3 blockers or silencing. These findings highlight K<sub>v</sub>1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 845","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scisignal.adg4124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1126/scisignal.adr5475
Amy E. Baek
Secreted factors from pyroptotic cells can promote wound repair.
热释细胞分泌的因子可促进伤口修复。
{"title":"Pyroptosis does damage control","authors":"Amy E. Baek","doi":"10.1126/scisignal.adr5475","DOIUrl":"10.1126/scisignal.adr5475","url":null,"abstract":"<div >Secreted factors from pyroptotic cells can promote wound repair.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 845","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1126/scisignal.adn6052
Justin W. Jackson, Frederick C. Streich Jr., Ajai Pal, George Coricor, Chris Boston, Christopher T. Brueckner, Kaleigh Canonico, Christopher Chapron, Shaun Cote, Kevin B. Dagbay, Francis T. Danehy Jr., Mania Kavosi, Sandeep Kumar, Susan Lin, Christopher Littlefield, Kailyn Looby, Rohan Manohar, Constance J. Martin, Marcie Wood, Agatha Zawadzka, Stefan Wawersik, Samantha B. Nicholls, Abhishek Datta, Alan Buckler, Thomas Schürpf, Gregory J. Carven, Mohammed Qatanani, Adam I. Fogel
Inhibitors of the transforming growth factor–β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β–binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-β1 presented by LTBPs but did not bind to TGF-β1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-β1 that is not accessible on GARP- or LRRC33-presented TGF-β1, explaining the antibody’s selectivity for LTBP-complexed TGF-β1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-β1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-β inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-β1 as an approach for treating fibrosis.
{"title":"An antibody that inhibits TGF-β1 release from latent extracellular matrix complexes attenuates the progression of renal fibrosis","authors":"Justin W. Jackson, Frederick C. Streich Jr., Ajai Pal, George Coricor, Chris Boston, Christopher T. Brueckner, Kaleigh Canonico, Christopher Chapron, Shaun Cote, Kevin B. Dagbay, Francis T. Danehy Jr., Mania Kavosi, Sandeep Kumar, Susan Lin, Christopher Littlefield, Kailyn Looby, Rohan Manohar, Constance J. Martin, Marcie Wood, Agatha Zawadzka, Stefan Wawersik, Samantha B. Nicholls, Abhishek Datta, Alan Buckler, Thomas Schürpf, Gregory J. Carven, Mohammed Qatanani, Adam I. Fogel","doi":"10.1126/scisignal.adn6052","DOIUrl":"10.1126/scisignal.adn6052","url":null,"abstract":"<div >Inhibitors of the transforming growth factor–β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β–binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-β1 presented by LTBPs but did not bind to TGF-β1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-β1 that is not accessible on GARP- or LRRC33-presented TGF-β1, explaining the antibody’s selectivity for LTBP-complexed TGF-β1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-β1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-β inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-β1 as an approach for treating fibrosis.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 844","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1126/scisignal.ado5279
Boris Hinz
In this issue of Science Signaling, Jackson et al. present a new antibody strategy to—quite literally—strap transforming growth factor–β1 (TGF-β1) to latent complexes in the extracellular matrix. The antibody has no effect on latent TGF-β1 presented on the surface of immune cells and thus allows targeting of the detrimental effects of TGF-β1 in fibrosis without affecting its beneficial immune-suppressing activities.
{"title":"More Velcro for the TGF-β1 straitjacket: A new antibody straps latent TGF-β1 to the matrix","authors":"Boris Hinz","doi":"10.1126/scisignal.ado5279","DOIUrl":"10.1126/scisignal.ado5279","url":null,"abstract":"<div >In this issue of <i>Science Signaling</i>, Jackson <i>et al.</i> present a new antibody strategy to—quite literally—strap transforming growth factor–β1 (TGF-β1) to latent complexes in the extracellular matrix. The antibody has no effect on latent TGF-β1 presented on the surface of immune cells and thus allows targeting of the detrimental effects of TGF-β1 in fibrosis without affecting its beneficial immune-suppressing activities.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 844","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1126/scisignal.adr3505
Leslie K. Ferrarelli
Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.
阿片类药物在成瘾的前馈回路中触发奖赏回路轴突的髓鞘绝缘。
{"title":"Insulated by opioids","authors":"Leslie K. Ferrarelli","doi":"10.1126/scisignal.adr3505","DOIUrl":"10.1126/scisignal.adr3505","url":null,"abstract":"<div >Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 843","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1126/scisignal.abq7038
Yusman Manchanda, Liliane ElEid, Affiong I. Oqua, Zenouska Ramchunder, Jiyoon Choi, Maria M. Shchepinova, Guy A. Rutter, Asuka Inoue, Edward W. Tate, Ben Jones, Alejandra Tomas
Mini-G proteins are engineered, thermostable variants of Gα subunits designed to stabilize G protein–coupled receptors (GPCRs) in their active conformations. Because of their small size and ease of use, they are popular tools for assessing GPCR behaviors in cells, both as reporters of receptor coupling to Gα subtypes and for cellular assays to quantify compartmentalized signaling at various subcellular locations. Here, we report that overexpression of mini-G proteins with their cognate GPCRs disrupted GPCR endocytic trafficking and associated intracellular signaling. In cells expressing the Gαs-coupled GPCR glucagon-like peptide 1 receptor (GLP-1R), coexpression of mini-Gs, a mini-G protein derived from Gαs, blocked β-arrestin 2 recruitment and receptor internalization and disrupted endosomal GLP-1R signaling. These effects did not involve changes in receptor phosphorylation or lipid nanodomain segregation. Moreover, we found that mini-G proteins derived from Gαi and Gαq also inhibited the internalization of GPCRs that couple to them. Finally, we developed an alternative intracellular signaling assay for GLP-1R using a nanobody specific for active Gαs:GPCR complexes (Nb37) that did not affect GLP-1R internalization. Our results have important implications for designing methods to assess intracellular GPCR signaling.
{"title":"Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling","authors":"Yusman Manchanda, Liliane ElEid, Affiong I. Oqua, Zenouska Ramchunder, Jiyoon Choi, Maria M. Shchepinova, Guy A. Rutter, Asuka Inoue, Edward W. Tate, Ben Jones, Alejandra Tomas","doi":"10.1126/scisignal.abq7038","DOIUrl":"10.1126/scisignal.abq7038","url":null,"abstract":"<div >Mini-G proteins are engineered, thermostable variants of Gα subunits designed to stabilize G protein–coupled receptors (GPCRs) in their active conformations. Because of their small size and ease of use, they are popular tools for assessing GPCR behaviors in cells, both as reporters of receptor coupling to Gα subtypes and for cellular assays to quantify compartmentalized signaling at various subcellular locations. Here, we report that overexpression of mini-G proteins with their cognate GPCRs disrupted GPCR endocytic trafficking and associated intracellular signaling. In cells expressing the Gα<sub>s</sub>-coupled GPCR glucagon-like peptide 1 receptor (GLP-1R), coexpression of mini-G<sub>s</sub>, a mini-G protein derived from Gα<sub>s</sub>, blocked β-arrestin 2 recruitment and receptor internalization and disrupted endosomal GLP-1R signaling. These effects did not involve changes in receptor phosphorylation or lipid nanodomain segregation. Moreover, we found that mini-G proteins derived from Gα<sub>i</sub> and Gα<sub>q</sub> also inhibited the internalization of GPCRs that couple to them. Finally, we developed an alternative intracellular signaling assay for GLP-1R using a nanobody specific for active Gα<sub>s</sub>:GPCR complexes (Nb37) that did not affect GLP-1R internalization. Our results have important implications for designing methods to assess intracellular GPCR signaling.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 843","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC). Using cell cultures, xenografts, and patient-derived explant models, we found that the inhibition of upstream Hippo-pathway kinases MST1 and MST2 or expression of a constitutively active YAP mutant impeded ccRCC proliferation and decreased gene expression mediated by the transcription factor NF-κB. Mechanistically, the NF-κB subunit p65 bound to the transcriptional cofactor TEAD to facilitate NF-κB–target gene expression that promoted cell proliferation. However, by competing for TEAD, YAP disrupted its interaction with NF-κB and prompted the dissociation of p65 from target gene promoters, thereby inhibiting NF-κB transcriptional programs. This cross-talk between the Hippo and NF-κB pathways in ccRCC suggests that targeting the Hippo-YAP axis in an atypical manner—that is, by activating YAP—may be a strategy for slowing tumor growth in patients.
{"title":"YAP represses the TEAD–NF-κB complex and inhibits the growth of clear cell renal cell carcinoma","authors":"Zhongbo Li, Peng Su, Miao Yu, Xufeng Zhang, Yaning Xu, Tianwei Jia, Penghe Yang, Chenmiao Zhang, Yanan Sun, Xin Li, Huijie Yang, Yinlu Ding, Ting Zhuang, Haiyang Guo, Jian Zhu","doi":"10.1126/scisignal.adk0231","DOIUrl":"10.1126/scisignal.adk0231","url":null,"abstract":"<div >The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC). Using cell cultures, xenografts, and patient-derived explant models, we found that the inhibition of upstream Hippo-pathway kinases MST1 and MST2 or expression of a constitutively active YAP mutant impeded ccRCC proliferation and decreased gene expression mediated by the transcription factor NF-κB. Mechanistically, the NF-κB subunit p65 bound to the transcriptional cofactor TEAD to facilitate NF-κB–target gene expression that promoted cell proliferation. However, by competing for TEAD, YAP disrupted its interaction with NF-κB and prompted the dissociation of p65 from target gene promoters, thereby inhibiting NF-κB transcriptional programs. This cross-talk between the Hippo and NF-κB pathways in ccRCC suggests that targeting the Hippo-YAP axis in an atypical manner—that is, by activating YAP—may be a strategy for slowing tumor growth in patients.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 843","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scisignal.adk0231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1126/scisignal.adp5354
Andreas Papassotiropoulos, Dominique J.-F. de Quervain
WWC1 is a scaffolding protein in the evolutionarily conserved Hippo signaling network and is genetically linked to human memory and synaptic plasticity. In the archives of Science Signaling, Stepan et al. demonstrate the translational potential of modulating WWC1 through pharmacological inhibition of Hippo-pathway kinases to enhance cognition.
{"title":"Tweaking synaptic plasticity: Deciphering the role of WWC1 in memory opens new therapeutic horizons","authors":"Andreas Papassotiropoulos, Dominique J.-F. de Quervain","doi":"10.1126/scisignal.adp5354","DOIUrl":"10.1126/scisignal.adp5354","url":null,"abstract":"<div >WWC1 is a scaffolding protein in the evolutionarily conserved Hippo signaling network and is genetically linked to human memory and synaptic plasticity. In the archives of <i>Science Signaling</i>, Stepan <i>et al.</i> demonstrate the translational potential of modulating WWC1 through pharmacological inhibition of Hippo-pathway kinases to enhance cognition.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"17 842","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号