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The PavMYB.C2-UFGT module contributes to fruit coloration via modulating anthocyanin biosynthesis in sweet cherry. PavMYB。C2-UFGT模块通过调节甜樱桃花青素的生物合成来促进果实的着色。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-17 DOI: 10.1371/journal.pgen.1011761
Yangang Pei, Wanjia Tang, Yidi Huang, Hongfen Li, Xiaowei Liu, Hongxu Chen, Runmei He, Wenyi Niu, Quanyan Du, Yizhe Chu, Heng Deng, Mingchun Liu, Ronggao Gong
{"title":"The PavMYB.C2-UFGT module contributes to fruit coloration via modulating anthocyanin biosynthesis in sweet cherry.","authors":"Yangang Pei, Wanjia Tang, Yidi Huang, Hongfen Li, Xiaowei Liu, Hongxu Chen, Runmei He, Wenyi Niu, Quanyan Du, Yizhe Chu, Heng Deng, Mingchun Liu, Ronggao Gong","doi":"10.1371/journal.pgen.1011761","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011761","url":null,"abstract":"<p><p>Anthocyanins, vital secondary metabolites responsible for fruit coloration and health benefits, yet the genetic mechanisms regulating anthocyanin biosynthesis in fruits remain incompletely understood. In this study, we conducted a metabolomic analysis that revealed both the total anthocyanin content and the relative abundance of individual anthocyanin species are critical contributors of the color variation observed between yellow- and dark red-fruited cultivars. Integrating transcriptomic data with metabolic profiles, we identified a gene module central to anthocyanin biosynthesis, with PavMYB.C2 emerging as a key transcriptional activator. Functional validation through overexpression and silencing of PavMYB.C2 in cherry fruit confirmed its essential role in regulating both total anthocyanin and cyanidin-3-glucoside (Cy3G) levels. Furthermore, PavMYB.C2 upregulates transcription of the anthocyanin biosynthetic gene UFGT via its serine (S) 68 residue within the MYB domain, leading to enhanced Cy3G accumulation. These findings highlight the PavMYB.C2-UFGT regulatory module as a critical determinant of fruit coloration, offering potential avenues for improving fruit quality through genetic manipulation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011761"},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan. 胰岛素敏感果蝇胰岛素样受体突变体重塑蛋氨酸代谢以延长寿命。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-16 DOI: 10.1371/journal.pgen.1011640
Marc Tatar, Wenjing Zheng, Shweta Yadav, Rochele Yamamoto, Noelle Curtis-Joseph, Shengxi Li, Lin Wang, Andrey A Parkhitko
{"title":"An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.","authors":"Marc Tatar, Wenjing Zheng, Shweta Yadav, Rochele Yamamoto, Noelle Curtis-Joseph, Shengxi Li, Lin Wang, Andrey A Parkhitko","doi":"10.1371/journal.pgen.1011640","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011640","url":null,"abstract":"<p><p>Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, we recently developed a series of Drosophila insulin-like receptor (dInr) mutants with single amino acid substitutions that extend lifespan but differentially affect insulin sensitivity, growth and reproduction. Transheterozygotes of canonical dInr mutants (Type I) extend longevity and are insulin-resistant, small and weakly fecund. In contrast, a dominant mutation (dInr353, Type II) within the Kinase Insert Domain (KID) robustly extends longevity but is insulin-sensitive, full-sized, and highly fecund. We applied transcriptome and metabolome analyses to explore how dInr353 slows aging without insulin resistance. Type I and II mutants overlap in many pathways but also produce distinct transcriptomic profiles that include differences in innate immune and reproductive functions. In metabolomic analyses, the KID mutant dInr353 reprograms methionine metabolism in a way that phenocopies dietary methionine restriction, in contrast to canonical mutants which are characterized by upregulation of the transsulfuration pathway. Because abrogation of S-adenosylhomocysteine hydrolase blocks the longevity benefit conferred by dInr353, we conclude the methionine cycle reprogramming of Type II is sufficient to slow aging. Metabolomic analysis further revealed the Type II mutant is metabolically flexible: unlike aged wildtype, aged dInr353 adults can reroute methionine toward the transsulfuration pathway, while Type I mutant flies upregulate the transsulfuration pathway continuously from young age. Altered insulin/insulin growth factor signaling has the potential to slow aging without the complications of insulin resistance by modulating methionine cycle dynamics.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011640"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monkeyflower (Mimulus) uncovers the evolutionary basis of the eukaryote telomere sequence variation. 猴花揭示了真核生物端粒序列变异的进化基础。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-16 eCollection Date: 2025-06-01 DOI: 10.1371/journal.pgen.1011738
Surbhi Kumawat, Askhan Shametov, Liia R Valeeva, Yoonha Ju, Irene Martinez, Dhenugen Logeswaran, Hongfei Chen, Jenn M Coughlan, Julian J-L Chen, Yao-Wu Yuan, James M Sobel, Dal-Hoe Koo, Eugene V Shakirov, Jae Young Choi
{"title":"Monkeyflower (Mimulus) uncovers the evolutionary basis of the eukaryote telomere sequence variation.","authors":"Surbhi Kumawat, Askhan Shametov, Liia R Valeeva, Yoonha Ju, Irene Martinez, Dhenugen Logeswaran, Hongfei Chen, Jenn M Coughlan, Julian J-L Chen, Yao-Wu Yuan, James M Sobel, Dal-Hoe Koo, Eugene V Shakirov, Jae Young Choi","doi":"10.1371/journal.pgen.1011738","DOIUrl":"10.1371/journal.pgen.1011738","url":null,"abstract":"<p><p>Telomeres are nucleoprotein complexes with crucial role of protecting chromosome ends. Because of its vital functions, components of the telomere, including its sequence, should be under strong evolutionary constraint. Yet across the tree of life there are numerous examples of telomere sequence variation and the evolutionary mechanism driving this diversification is unclear. Here, we studied the telomeres in Mimulus by investigating the noncoding telomerase RNA (TR), which is a core component of the telomere maintenance complex and determines the telomere sequence in eukaryotes. We conducted de novo transcriptomics and genome analysis of 18 species, and discovered Mimulus has evolved at least three different telomere sequences: (AAACCCT)n, (AAACCCG)n, and (AAACCG)n. We discovered several species with TR duplications, implying functional consequences that could influence telomere evolution. For instance, M. lewisii harbored two sequence-divergent TR paralogs while its sister species the paralog had pseudogenized. Nanopore-sequencing and fluorescence in situ hybridization indicated M. lewisii had a sequence heterogeneous telomere, and Telomeric Repeat Amplification Protocol combined with Terminal Restriction Fragment analysis confirmed the telomerase can use both TR paralogs for telomere synthesis. Interestingly in closely related species M. cardinalis, TR was also duplicated and both paralogs were expressed but its telomere consisted of a single telomere repeat. Evolutionary analysis indicated the TR paralogs arose from an ancient duplication, which also underlies the evolutionary origin of multiple Mimulus species with divergent telomere sequences. We propose sequence variation in eukaryotic telomeres arises from an evolutionary process involving TR duplication, sequence divergence, and loss of TR paralog.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011738"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Aspergillus nidulans velvet domain containing transcription factor VeA is shuttled from cytoplasm into nucleus during vegetative growth and stays there for sexual development, but has to return into cytoplasm for asexual development. 含转录因子VeA的中性曲霉丝绒结构域在营养生长过程中从细胞质进入细胞核并停留在那里进行性发育,但在无性发育过程中必须返回细胞质。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-16 eCollection Date: 2025-06-01 DOI: 10.1371/journal.pgen.1011687
Anja Strohdiek, Anna M Köhler, Rebekka Harting, Helena Stupperich, Jennifer Gerke, Emmanouil Bastakis, Piotr Neumann, Yasar L Ahmed, Ralf Ficner, Gerhard H Braus
{"title":"The Aspergillus nidulans velvet domain containing transcription factor VeA is shuttled from cytoplasm into nucleus during vegetative growth and stays there for sexual development, but has to return into cytoplasm for asexual development.","authors":"Anja Strohdiek, Anna M Köhler, Rebekka Harting, Helena Stupperich, Jennifer Gerke, Emmanouil Bastakis, Piotr Neumann, Yasar L Ahmed, Ralf Ficner, Gerhard H Braus","doi":"10.1371/journal.pgen.1011687","DOIUrl":"10.1371/journal.pgen.1011687","url":null,"abstract":"<p><p>Survival of multicellular organisms requires the coordinated interplay between networks regulating gene expression and controlled intracellular transport of respective regulators. Velvet domain proteins are fungal transcription factors, which form various heterodimers and play key roles in controlling early developmental decisions towards more either asexual or sexual differentiation. VeA is the central subunit of the trimeric velvet complex VelB-VeA-LaeA, which links transcriptional to epigenetic control for the coordination of fungal developmental programs to specific secondary metabolite synthesis. Nuclear localization of the VeA bridging factor is carefully controlled in fungi. In this work we demonstrate that VeA carries three nuclear localization signals NLS1, NLS2 and NLS3, which all contribute to nuclear import. We show that VeA has an additional nuclear export sequence (NES) which provides a shuttle function to allow the cell to relocate VeA to the cytoplasm. VeA is nuclear during vegetative growth, but has to be exported from the nucleus to allow and promote asexual development. In contrast, progression of the sexual pathway requires continuous nuclear VeA localization. Our work shows that an accurate nuclear import and export control of velvet proteins is further connected to specific stability control mechanism as prerequisites for fungal development and secondary metabolism. These results illustrate the various complex mutual dependencies of velvet regulatory proteins for coordinating fungal development and secondary metabolism.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011687"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Basal association of a transcription factor favors early gene expression. 转录因子的基础关联有利于早期基因表达。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-16 DOI: 10.1371/journal.pgen.1011710
Sandrine Pinheiro, Mariona Nadal-Ribelles, Carme Solé, Vincent Vincenzetti, Yves Dusserre, Francesc Posas, Serge Pelet
{"title":"Basal association of a transcription factor favors early gene expression.","authors":"Sandrine Pinheiro, Mariona Nadal-Ribelles, Carme Solé, Vincent Vincenzetti, Yves Dusserre, Francesc Posas, Serge Pelet","doi":"10.1371/journal.pgen.1011710","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011710","url":null,"abstract":"<p><p>Responses to extracellular signals via Mitogen-Activated Protein Kinase (MAPK) pathways control complex transcriptional programs where hundreds of genes are induced at a desired level with a specific timing. Gene expression regulation is largely encoded in the promoter of the gene, which harbors numerous transcription factor binding sites. In the mating MAPK pathway of Saccharomyces cerevisiae, one major transcription factor, Ste12, controls the chronology of gene expression necessary for the fusion of two haploid cells. Because endogenous promoters encode a large diversity of Ste12 binding sites (PRE), we engineered synthetic promoters to decipher the rules that dictate mating gene induction. Conformations of PRE dimers that allow efficient gene expression were identified. The strength of binding of Ste12 to the PRE and the distance of the binding sites to the core promoter modulate the level of induction. The speed of activation is ensured by favoring a basal association of Ste12 by using a strong dimer of PRE located in a nucleosome depleted region.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011710"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell cycle dependent methylation of Dam1 contributes to kinetochore integrity and faithful chromosome segregation. 细胞周期依赖性的Dam1甲基化有助于着丝点完整性和忠实的染色体分离。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-16 DOI: 10.1371/journal.pgen.1011760
Prashant K Mishra, Wei-Chun Au, John S Choy, Pedro G Castineira, Afsa Khawar, Chloé Tessier, Sudipto Das, Andresson Thorkell, Peter H Thorpe, Elaine Yeh, Kerry S Bloom, Munira A Basrai
{"title":"Cell cycle dependent methylation of Dam1 contributes to kinetochore integrity and faithful chromosome segregation.","authors":"Prashant K Mishra, Wei-Chun Au, John S Choy, Pedro G Castineira, Afsa Khawar, Chloé Tessier, Sudipto Das, Andresson Thorkell, Peter H Thorpe, Elaine Yeh, Kerry S Bloom, Munira A Basrai","doi":"10.1371/journal.pgen.1011760","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011760","url":null,"abstract":"<p><p>The kinetochore, a megadalton structure composed of centromeric (CEN) DNA and protein complexes, is required for faithful chromosome segregation in eukaryotes. The evolutionarily conserved Dam1/DASH complex (Ska1 in metazoans) is one of the essential protein sub-complexes of the budding yeast kinetochore. Previous studies showed that methylation of lysine residue 233 in Dam1 by Set1 is important for haploid growth as mutation of lysine 233 to alanine results in lethality. In this study, we report that Set1-mediated cell cycle dependent Dam1 lysine methylation contributes to kinetochore assembly and chromosomal stability. Our results show that Dam1 methylation is cell cycle regulated with the highest levels of methylation in metaphase. Consistent with these results, co-immunoprecipitation experiments revealed an interaction between Dam1 with Set1 in metaphase cells. Set1 has been shown to colocalize with Jhd2, a histone lysine demethylase which demethylates Set1-methylated histones. Affinity purification-based mass spectroscopy of Jhd2 associated proteins identified seven of the ten subunits of the Dam1 complex; an association of Jhd2 with non-histone proteins, such as Dam1 has not been previously reported. We confirmed the interaction of Jhd2 with Dam1 and showed that cells overexpressing JHD2 exhibit reduced levels of methylated lysine in Dam1 in wild type and UBP8 deletion strains, growth defects in kinetochore mutants, reduced levels of kinetochore proteins at CEN chromatin, defects in kinetochore biorientation and chromosome missegregation. In summary, we have shown that cell cycle dependent methylation of Dam1 plays a crucial role in the maintenance of kinetochore assembly for faithful chromosome segregation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011760"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Titin-Truncating variants predispose to dilated cardiomyopathy in populations genetically similar to african and european reference populations. 在遗传上与非洲和欧洲参考人群相似的人群中,titin截断变异体易患扩张性心肌病。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-13 DOI: 10.1371/journal.pgen.1011727
John DePaolo, Marc R Bornstein, Renae Judy, Sarah Abramowitz, Shefali S Verma, Michael G Levin, Zoltan Arany, Scott M Damrauer
{"title":"Titin-Truncating variants predispose to dilated cardiomyopathy in populations genetically similar to african and european reference populations.","authors":"John DePaolo, Marc R Bornstein, Renae Judy, Sarah Abramowitz, Shefali S Verma, Michael G Levin, Zoltan Arany, Scott M Damrauer","doi":"10.1371/journal.pgen.1011727","DOIUrl":"10.1371/journal.pgen.1011727","url":null,"abstract":"<p><p>The effect of high percentage spliced in (hiPSI) TTN truncating variants (TTNtvs) on risk of dilated cardiomyopathy (DCM) has historically been studied among population subgroups defined by genetic similarity to European reference populations. This has raised questions about the effect of TTNtvs in diverse populations, especially among individuals genetically similar to African reference populations. To determine the effect of TTNtvs on cardiovascular disease risk, we leveraged whole exome sequencing and electronic health record data from 43,731 Penn Medicine Biobank (PMBB) participants recruited from across the Penn Medicine healthcare system. Fraction of genetic similarity to the 1000 Genomes Project (1000G) African (AFR) reference population was determined using ADMIXTURE analysis. Logistic regression was performed to evaluate the association of hiPSI TTNtvs with prevalent DCM and atrial fibrillation (Afib), and linear regression was used to evaluate the association with reduced left ventricular ejection fraction (LVEF) either using dichotomized genetically similar population subgroup analysis or integrating ADMIXTURE population fraction. When individuals were assigned to population subgroups based on genetic similarity to the 1000G reference populations, hiPSI TTNtvs conferred significant risk of DCM among those genetically similar to the 1000G European (EUR) reference population (OR=6.12, 95% confidence intervals [CI] 4.33 to 8.65, P < 0.001) and individuals genetically similar to the AFR reference population (OR=3.44, 95% CI 1.97 to 5.99, P < 0.001). These results were consistent when considering the effect of change in fraction of similarity to the African reference population by ADMIXTURE as a continuous variable. Similar results were observed for the effect of TTNtvs on Afib and LVEF. Our findings demonstrate that TTNtvs are associated with increased risk of DCM, reduced LVEF, and Afib among a diverse cohort. There is no significant difference in effect of TTNtvs across fractions of similarity to the AFR reference population suggesting genetic background should not be considered when screening individuals for titin-related cardiovascular disease.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011727"},"PeriodicalIF":4.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss of FIC-1-mediated AMPylation activates the UPRER and upregulates cytosolic HSP70 chaperones to suppress polyglutamine toxicity. fic -1介导的AMPylation缺失激活UPRER并上调胞内HSP70伴侣抑制多聚谷氨酰胺毒性。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-13 DOI: 10.1371/journal.pgen.1011723
Kate M Van Pelt, Matthias C Truttmann
{"title":"Loss of FIC-1-mediated AMPylation activates the UPRER and upregulates cytosolic HSP70 chaperones to suppress polyglutamine toxicity.","authors":"Kate M Van Pelt, Matthias C Truttmann","doi":"10.1371/journal.pgen.1011723","DOIUrl":"10.1371/journal.pgen.1011723","url":null,"abstract":"<p><p>Targeted regulation of cellular proteostasis machinery represents a promising strategy for the attenuation of pathological protein aggregation. Recent work suggests that the unfolded protein response in the endoplasmic reticulum (UPRER) directly regulates the aggregation and toxicity of expanded polyglutamine (polyQ) proteins. However, the mechanisms underlying this phenomenon remain poorly understood. In this study, we report that perturbing ER homeostasis in Caenorhabditis elegans through the depletion of either BiP ortholog, hsp-3 or hsp-4, causes developmental arrest in worms expressing aggregation-prone polyQ proteins. This phenotype is rescued by the genetic deletion of the conserved UPRER regulator, FIC-1. We demonstrate that the beneficial effects of fic-1 knock-out (KO) extend into adulthood, where the loss of FIC-1-mediated protein AMPylation in polyQ-expressing animals is sufficient to prevent declines in fitness and lifespan. We further show that loss of hsp-3 and hsp-4 leads to distinct, but complementary transcriptomic responses to ER stress involving all three UPRER stress sensors (IRE-1, PEK-1, and ATF-6). We identify the cytosolic HSP70 family chaperone F44E5.4, whose expression is increased in fic-1-deficient animals upon ER dysregulation, as a key effector suppressing polyQ toxicity. Over-expression of F44E5.4, but not other HSP70 family chaperones, is sufficient to rescue developmental arrest in polyQ-expressing embryos upon hsp-3 knock-down. We further show that knock-down of ire-1 or atf-6 blocks the upregulation of F44E5.4 in fic-1-deficient worms. Taken together, our findings support a model in which the loss of FIC-1-mediated AMPylation engages UPRER signaling to upregulate cytosolic chaperone activity in response to polyQ toxicity.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011723"},"PeriodicalIF":4.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration. 可视化雄激素信号并评估其与典型Wnt信号通路在前列腺发育、形态发生和再生中的相互作用。
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-13 DOI: 10.1371/journal.pgen.1011756
Yao Mawulikplimi Adzavon, Dong-Hoon Lee, Alex Hiroto, Tae Ju Park, Gaeul Chu, Yunjeong Kim, Kristoffer Nikias, Cheong-Wun Kim, Dexter Hoi Long Leung, Chenmiao Liu, Hong Zeng, Zijie Sun
{"title":"Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration.","authors":"Yao Mawulikplimi Adzavon, Dong-Hoon Lee, Alex Hiroto, Tae Ju Park, Gaeul Chu, Yunjeong Kim, Kristoffer Nikias, Cheong-Wun Kim, Dexter Hoi Long Leung, Chenmiao Liu, Hong Zeng, Zijie Sun","doi":"10.1371/journal.pgen.1011756","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011756","url":null,"abstract":"<p><p>The androgen receptor (AR) is a nuclear hormone receptor, and its activation through binding to androgens is essential for prostate development, morphogenesis, growth, and tumorigenesis. Although significant efforts have been devoted to understanding the critical role of AR, the cellular properties and functions of the AR-expressing cells acting as prostatic progenitors in controlling prostatic cell differentiation and growth still remain elusive. Additionally, dynamic paracrine interactions between urogenital mesenchyme and epithelia initiated by the AR activation through prostate development are also largely unknown. Recently, we modified the mouse Ar gene locus, which enables us to genetically label AR-expressing cells spatiotemporally and trace them through prostate development, morphogenesis, and growth in combination with a double-fluorescent reporter mouse model. The membrane-bound green fluorescent protein (mGFP)-expressing cells were revealed in both urogenital sinus mesenchyme (UGM) and epithelium (UGE) at embryonic day E18.5 when Tamoxifen was administrated at E13.5 to activate CreER recombinase directed by the endogenous Ar promoter. The AR-expressing cells and their descendants were further detected at postnatal days 10, 35, and 56, and through three cycles of prostatic regeneration by repeated androgen deprivation and replacement. Deletion of β-catenin through the AR-driven CreER in embryonic AR-expressing cells impairs prostate development and morphogenesis. Specifically, altered β-catenin expression results in loss of prostatic glandular cell polarity and activation of Fas death signaling pathways. These lines of experimental evidence demonstrate the biological relevance and significance of this new genetic tool to assess and visualize AR-mediated signaling pathways through prostatic development, growth, and tumorigenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011756"},"PeriodicalIF":4.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Root remodeling mechanisms and salt tolerance trade-offs: The roles of HKT1, TMAC2, and TIP2;2 in Arabidopsis. 拟南芥根系重塑机制和耐盐性权衡:HKT1、TMAC2和TIP2;2在拟南芥中的作用
IF 4 2区 生物学
PLoS Genetics Pub Date : 2025-06-11 DOI: 10.1371/journal.pgen.1011713
Nouf O Alshareef, Vanessa J Melino, Noha Saber, Annamaria De Rosa, Elodie Rey, Jian You Wang, Salim AlBabili, Caitlin Byrt, Mark A Tester, Magdalena M Julkowska
{"title":"Root remodeling mechanisms and salt tolerance trade-offs: The roles of HKT1, TMAC2, and TIP2;2 in Arabidopsis.","authors":"Nouf O Alshareef, Vanessa J Melino, Noha Saber, Annamaria De Rosa, Elodie Rey, Jian You Wang, Salim AlBabili, Caitlin Byrt, Mark A Tester, Magdalena M Julkowska","doi":"10.1371/journal.pgen.1011713","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011713","url":null,"abstract":"<p><p>Plant responses to salt stress involve regulatory networks integrating ion transport, hormonal signaling, and root system architecture remodeling. A key adaptive mechanism is the regulation of sodium (Na⁺) transport by Class 1 HKT1 transporters, which compertamentalize Na⁺ in non-photosynthetic tissues. High HKT1 expression reduces Na+ accumulation in shoots, leading to increased salt tolerance, but simultaneously results in reduced lateral root development. In this study, we explored transcriptional responses that are altered by high HKT1 expression in root stelle in two Arabidopsis backgrounds, Col-0 and C24. We identified TMAC2, a negative ABA regulator, and TIP2:2, a tonoplast aquaporin, as key modulators of root development under salt stress. While TIP2:2 function was conserved, TMAC2 exhibited genotype-specific effects on ABA accumulation and HKT1-mediated salt sensitivity. Co-expression of TMAC2 and HKT1 in Col-0 upregulated ABI4 and ABI5, linking Na⁺ transport to ABA signaling. Our findings underscore genetic context in shaping salt responses and provide molecular targets for enhancing root plasticity under stress.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011713"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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