PLoS GeneticsPub Date : 2025-02-18eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011534
Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders
{"title":"Functional constraints of wtf killer meiotic drivers.","authors":"Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders","doi":"10.1371/journal.pgen.1011534","DOIUrl":"10.1371/journal.pgen.1011534","url":null,"abstract":"<p><p>Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver- heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver- gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011534"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450750","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}
PLoS GeneticsPub Date : 2025-02-18eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011606
Allison C Hullinger, Virginia E Green, Catherine A Klancher, Triana N Dalia, Ankur B Dalia
{"title":"Two transmembrane transcriptional regulators coordinate to activate chitin-induced natural transformation in Vibrio cholerae.","authors":"Allison C Hullinger, Virginia E Green, Catherine A Klancher, Triana N Dalia, Ankur B Dalia","doi":"10.1371/journal.pgen.1011606","DOIUrl":"10.1371/journal.pgen.1011606","url":null,"abstract":"<p><p>Transcriptional regulators are a broad class of proteins that alter gene expression in response to environmental stimuli. Transmembrane transcriptional regulators (TTRs) are a subset of transcriptional regulators in bacteria that can directly regulate gene expression while remaining anchored in the membrane. Whether this constraint impacts the ability of TTRs to bind their DNA targets remains unclear. Vibrio cholerae uses two TTRs, ChiS and TfoS, to activate horizontal gene transfer by natural transformation in response to chitin by inducing the tfoR promoter (PtfoR). While TfoS was previously shown to bind and regulate PtfoR directly, the role of ChiS in PtfoR activation remains unclear. Here, we show that ChiS directly binds PtfoR upstream of TfoS, and that ChiS directly interacts with TfoS. By independently disrupting ChiS-PtfoR and ChiS-TfoS interactions, we show that ChiS-PtfoR interactions play the dominant role in PtfoR activation. Correspondingly, we show that in the absence of ChiS, recruitment of the PtfoR locus to the membrane is sufficient for PtfoR activation when TfoS is expressed at native levels. Finally, we show that the overexpression of TfoS can bypass the need for ChiS for PtfoR activation. All together, these data suggest a model whereby ChiS both (1) recruits the PtfoR DNA locus to the membrane for TfoS and (2) directly interacts with TfoS, thereby recruiting it to the membrane-proximal promoter. This work furthers our understanding of the molecular mechanisms that drive chitin-induced responses in V. cholerae and more broadly highlights how the membrane-embedded localization of TTRs can impact their activity.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011606"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450755","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}
{"title":"The recombination landscape of introgression in yeast.","authors":"Enrique J Schwarzkopf, Nathan Brandt, Caiti Smukowski Heil","doi":"10.1371/journal.pgen.1011585","DOIUrl":"10.1371/journal.pgen.1011585","url":null,"abstract":"<p><p>Meiotic recombination is an evolutionary force that acts by breaking up genomic linkage, increasing the efficacy of selection. Recombination is initiated with a double-strand break which is resolved via a crossover, which involves the reciprocal exchange of genetic material between homologous chromosomes, or a non-crossover, which results in small tracts of non-reciprocal exchange of genetic material. Crossover and non-crossover rates vary between species, populations, individuals, and across the genome. In recent years, recombination rate has been associated with the distribution of ancestry derived from past interspecific hybridization (introgression) in a variety of species. We explore this interaction of recombination and introgression by sequencing spores and detecting crossovers and non-crossovers from two crosses of the yeast Saccharomyces uvarum. One cross is between strains which each contain introgression from their sister species, S. eubayanus, while the other cross has no introgression present. We find that the recombination landscape is significantly different between S. uvarum crosses, and that some of these differences can be explained by the presence of introgression in one cross. Crossovers are significantly reduced in heterozygous introgression compared to syntenic regions in the cross without introgression. This translates to reduced allele shuffling within introgressed regions, and an overall reduction of shuffling on most chromosomes with introgression compared to the syntenic regions and chromosomes without introgression. Our results suggest that hybridization can significantly influence the recombination landscape, and that the reduction in allele shuffling contributes to the initial purging of introgression in the generations following a hybridization event.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011585"},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411278","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}
PLoS GeneticsPub Date : 2025-02-10eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011570
Olivia A Gray, David B Witonsky, Jordan Jousma, Débora R Sobreira, Alexander Van Alstyne, Ru-Ting Huang, Yun Fang, Anna Di Rienzo
{"title":"Transcriptomic analysis of iPSC-derived endothelium reveals adaptations to high altitude hypoxia in energy metabolism and inflammation.","authors":"Olivia A Gray, David B Witonsky, Jordan Jousma, Débora R Sobreira, Alexander Van Alstyne, Ru-Ting Huang, Yun Fang, Anna Di Rienzo","doi":"10.1371/journal.pgen.1011570","DOIUrl":"10.1371/journal.pgen.1011570","url":null,"abstract":"<p><p>Tibetan adaptation to high-altitude hypoxia remains a classic example of Darwinian selection in humans. Amongst Tibetan populations, alleles in the EPAS1 gene - whose protein product, HIF-2α, is a central regulator of the hypoxia response - have repeatedly been shown to carry some of the strongest signals of positive selection in humans. However, selective sweep signals alone may only account for some of the phenotypes that differentiate high-altitude adapted populations from closely related lowlanders. Therefore, there is a pressing need to functionally probe adaptive alleles and their impact at both the locus-specific and genome-wide levels and across cell types to uncover the full range of beneficial traits. To this end, we established a library of induced pluripotent stem cells (iPSCs) derived from Tibetan and Han Chinese individuals, a robust model system allowing precise exploration of allelic effects on transcriptional responses, and we differentiated them into vascular endothelium. Using this system, we focus first on a hypoxia-dependent enhancer (ENH5) that contributes to the regulation of EPAS1 to investigate its locus-specific effects in endothelium. Then, to cast a wider net, we harness the same experimental system to compare the transcriptome of Tibetan and Han Chinese cells in hypoxia and find evidence that angiogenesis, energy metabolism and immune pathways differ between these two populations with different histories of long-term residence at high altitude. Coupled with evidence of polygenic adaptations targeting the same pathways, these results suggests that the observed transcriptional differences between the two populations were shaped by natural selection.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011570"},"PeriodicalIF":4.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392183","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}
PLoS GeneticsPub Date : 2025-02-07eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011560
Jorge Rodriguez-Grande, Yelina Ortiz, Daniel Garcia-Lopez, M Pilar Garcillán-Barcia, Fernando de la Cruz, Raul Fernandez-Lopez
{"title":"Encounter rates and engagement times limit the transmission of conjugative plasmids.","authors":"Jorge Rodriguez-Grande, Yelina Ortiz, Daniel Garcia-Lopez, M Pilar Garcillán-Barcia, Fernando de la Cruz, Raul Fernandez-Lopez","doi":"10.1371/journal.pgen.1011560","DOIUrl":"10.1371/journal.pgen.1011560","url":null,"abstract":"<p><p>Plasmid conjugation is a major route for the dissemination of antibiotic resistances and adaptive genes among bacterial populations. Obtaining precise conjugation rates is thus key to understanding how antibiotic resistances spread. Plasmid conjugation is typically modeled as a density-dependent process, where the formation of new transconjugants depends on the rate of encounters between donor and receptor cells. By analyzing conjugation dynamics at different cell concentrations, here we show that this assumption only holds at very low bacterial densities. At higher cell concentrations, conjugation becomes limited by the engagement time, the interval required between two successful matings. Plasmid conjugation therefore follows a Holling´s Type II functional response, characterized by the encounter rate and the engagement time, which represent, respectively, the density and frequency-dependent limits of plasmid transmission. Our results demonstrate that these parameters are characteristic of the transfer machinery, rather than the entire plasmid genome, and that they are robust to environmental and transcriptional perturbation. Precise parameterization of plasmid conjugation will contribute to better understanding the propagation dynamics of antimicrobial resistances.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011560"},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371334","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}
PLoS GeneticsPub Date : 2025-02-07eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011531
Ava C Wilson, Alison Rocco, Joe Chiles, Vinodh Srinivasasainagendra, Wassim Labaki, Deborah Meyers, Bertha Hidalgo, Marguerite R Irvin, Surya P Bhatt, Hemant Tiwari, Merry-Lynn McDonald
{"title":"Novel risk loci encompassing genes influencing STAT3, GPCR, and oxidative stress signaling are associated with co-morbid GERD and COPD.","authors":"Ava C Wilson, Alison Rocco, Joe Chiles, Vinodh Srinivasasainagendra, Wassim Labaki, Deborah Meyers, Bertha Hidalgo, Marguerite R Irvin, Surya P Bhatt, Hemant Tiwari, Merry-Lynn McDonald","doi":"10.1371/journal.pgen.1011531","DOIUrl":"10.1371/journal.pgen.1011531","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a leading cause of death globally. Gastroesophageal reflux disease (GERD) is a common comorbidity in COPD associated with worse pulmonary symptoms, reduced quality of life, and increased exacerbations and hospitalizations. GERD treatment in COPD is associated with a lower risk of exacerbations and mortality; however, it is not clear whether these findings can be attributed to aging populations where both diseases are likely to co-occur or reflect shared etiology. To test for the influence of common etiology in both diseases, we aimed to identify shared genetic etiology between GERD and COPD. We performed the first whole-genome sequence association analysis of comorbid GERD and COPD in 12,438 multi-ancestry participants. The co-heritability of GERD and COPD was 39.7% (h2 = 0.397, SE = 0.074) and we identified several ancestry-independent loci associated with co-morbid GERD and COPD (within LINC02493 and FRYL) known to be involved in oxidative stress and G protein-coupled receptor (GPCR) signaling mechanisms. We found several loci associated with co-morbid GERD and COPD previously associated with GERD or COPD individually, including HCG17, which plays a role in oxidative stress mechanisms. Gene set enrichment identified GPCR signaling pathways in co-morbid GERD and COPD loci. Rare variants in ZFP42, encoding key regulators of the IL6/STAT3 pathway, have been previously implicated with GI disorders and were associated with co-morbid GERD and COPD. We identified common genetic etiology for GERD in COPD which begins to provide a mechanistic foundation for the potential therapeutic utility of STAT3, oxidation, and GPCR signaling pathway modulators in both GERD and COPD.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011531"},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371349","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}
PLoS GeneticsPub Date : 2025-02-07eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011587
T Scott Carlew, Eric Brenya, Mahbuba Ferdous, Ishita Banerjee, Lauren Donnelly, Eric Heinze, Josie King, Briana Sexton, Randy F Lacey, Arkadipta Bakshi, Gladys Alexandre, Brad M Binder
{"title":"Ethylene signals through an ethylene receptor to modulate biofilm formation and root colonization in a beneficial plant-associated bacterium.","authors":"T Scott Carlew, Eric Brenya, Mahbuba Ferdous, Ishita Banerjee, Lauren Donnelly, Eric Heinze, Josie King, Briana Sexton, Randy F Lacey, Arkadipta Bakshi, Gladys Alexandre, Brad M Binder","doi":"10.1371/journal.pgen.1011587","DOIUrl":"10.1371/journal.pgen.1011587","url":null,"abstract":"<p><p>Ethylene is a plant hormone involved in many aspects of plant growth and development as well as responses to stress. The role of ethylene in plant-microbe interactions has been explored from the perspective of plants. However, only a small number of studies have examined the role of ethylene in microbes. We demonstrated that Azospirillum brasilense contains a functional ethylene receptor that we call Azospirillum Ethylene Response1 (AzoEtr1) after the nomenclature used in plants. AzoEtr1 directly binds ethylene with high affinity. Treating cells with ethylene or disrupting the receptor reduces biofilm formation and colonization of plant root surfaces. Additionally, RNA sequencing and untargeted metabolomics showed that ethylene causes wide-spread metabolic changes that affect carbon and nitrogen metabolism. One result is the accumulation of poly-hydroxybutyrate. Our data suggests a model in which ethylene from host plants alters the density of colonization by A. brasilense and re-wires its metabolism, suggesting that the bacterium implements an adaptation program upon sensing ethylene. These data provide potential new targets to regulate beneficial plant-microbe interactions.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011587"},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371337","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}
PLoS GeneticsPub Date : 2025-02-07eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011594
Thomas Juan, Tonatiuh Molina, Lihan Xie, Sofia Papadopoulou, Bárbara Cardoso, Shivam Govind Jha, Didier Y R Stainier
{"title":"A recombinase-activated ribozyme to knock down endogenous gene expression in zebrafish.","authors":"Thomas Juan, Tonatiuh Molina, Lihan Xie, Sofia Papadopoulou, Bárbara Cardoso, Shivam Govind Jha, Didier Y R Stainier","doi":"10.1371/journal.pgen.1011594","DOIUrl":"10.1371/journal.pgen.1011594","url":null,"abstract":"<p><p>Precise regulation of gene expression is essential to understand a wide range of biological processes. Control over gene expression can be achieved using site-directed recombinases and endonucleases whose efficiency is variable and dependent on the genomic context. Here, we develop a self-cleaving ribozyme-based tool to control mRNA levels of endogenous targets in zebrafish. Using an in vivo reporter strategy, we first show that inserting the T3H48 self-cleaving ribozyme in an intron enables rapid pre-mRNA cleavage, with up to 20-fold reduction in expression, and that this ribozyme displays superior activity compared with other ribozymes. We then inserted the T3H48 ribozyme in the second intron of the albino gene using a CRISPR/Cas9 strategy and observed a pigmentation phenotype similar to that in the mutant. Using a base-editing strategy to inactivate the ribozyme, we also show that this phenotype is reversible, illustrating the specificity of the approach. In addition, we generated a Flippase- and Cre-activatable version of the T3H48 ribozyme, called RiboFlip, to control the mRNA levels of the albino gene. RiboFlip activation induced mRNA knockdown and also recapitulated the albino mutant phenotype. Furthermore, we show that a Cre- and Dre-controllable Gal4/UAS reporter in the RiboFlip cassette can label knocked-down cells independently of the expression of the target gene. Altogether, we introduce the RiboFlip cassette as a flexible tool to control endogenous gene expression in a vertebrate model and as an alternative to existing conditional knockdown strategies.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011594"},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371331","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}
PLoS GeneticsPub Date : 2025-02-06eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011554
Longjun Pu, Jing Wang, Lars Nilsson, Lina Zhao, Chloe Williams, Guanqiao Chi, Jonathan D Gilthorpe, Simon Tuck, Johan Henriksson, Yi-Quan Tang, Sun Nyunt Wai, Changchun Chen
{"title":"Shaker/Kv1 potassium channel SHK-1 protects against pathogen infection and oxidative stress in C. elegans.","authors":"Longjun Pu, Jing Wang, Lars Nilsson, Lina Zhao, Chloe Williams, Guanqiao Chi, Jonathan D Gilthorpe, Simon Tuck, Johan Henriksson, Yi-Quan Tang, Sun Nyunt Wai, Changchun Chen","doi":"10.1371/journal.pgen.1011554","DOIUrl":"10.1371/journal.pgen.1011554","url":null,"abstract":"<p><p>The Shaker/Kv1 subfamily of voltage-gated potassium (K+) channels is essential for modulating membrane excitability. Their loss results in prolonged depolarization and excessive calcium influx. These channels have also been implicated in a variety of other cellular processes, but the underlying mechanisms remain poorly understood. Through comprehensive screening of K+ channel mutants in C. elegans, we discovered that shk-1 mutants are highly susceptible to bacterial pathogen infection and oxidative stress. This vulnerability is associated with reduced glycogen levels and substantial mitochondrial dysfunction, including decreased ATP production and dysregulated mitochondrial membrane potential under stress conditions. SHK-1 is predominantly expressed and functions in body wall muscle to maintain glycogen storage and mitochondrial homeostasis. RNA-sequencing data reveal that shk-1 mutants have decreased expression of a set of cation-transporting ATPases (CATP), which are crucial for maintaining electrochemical gradients. Intriguingly, overexpressing catp-3, but not other catp genes, restores the depolarization of mitochondrial membrane potential under stress and enhances stress tolerance in shk-1 mutants. This finding suggests that increased catp-3 levels may help restore electrochemical gradients disrupted by shk-1 deficiency, thereby rescuing the phenotypes observed in shk-1 mutants. Overall, our findings highlight a critical role for SHK-1 in maintaining stress tolerance by regulating glycogen storage, mitochondrial homeostasis, and gene expression. They also provide insights into how Shaker/Kv1 channels participate in a broad range of cellular processes.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011554"},"PeriodicalIF":4.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365534","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}
PLoS GeneticsPub Date : 2025-02-06eCollection Date: 2025-02-01DOI: 10.1371/journal.pgen.1011586
Buffy L Eldridge-Thomas, Jerome G Bohere, Chantal Roubinet, Alexandre Barthelemy, Tamsin J Samuels, Felipe Karam Teixeira, Golnar Kolahgar
{"title":"The transmembrane protein Syndecan is required for stem cell survival and maintenance of their nuclear properties.","authors":"Buffy L Eldridge-Thomas, Jerome G Bohere, Chantal Roubinet, Alexandre Barthelemy, Tamsin J Samuels, Felipe Karam Teixeira, Golnar Kolahgar","doi":"10.1371/journal.pgen.1011586","DOIUrl":"10.1371/journal.pgen.1011586","url":null,"abstract":"<p><p>Tissue maintenance is underpinned by resident stem cells whose activity is modulated by microenvironmental cues. Using Drosophila as a simple model to identify regulators of stem cell behaviour and survival in vivo, we have identified novel connections between the conserved transmembrane proteoglycan Syndecan, nuclear properties and stem cell function. In the Drosophila midgut, Syndecan depletion in intestinal stem cells results in their loss from the tissue, impairing tissue renewal. At the cellular level, Syndecan depletion alters cell and nuclear shape, and causes nuclear lamina invaginations and DNA damage. In a second tissue, the developing Drosophila brain, live imaging revealed that Syndecan depletion in neural stem cells results in nuclear envelope remodelling defects which arise upon cell division. Our findings reveal a new role for Syndecan in the maintenance of nuclear properties in diverse stem cell types.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011586"},"PeriodicalIF":4.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365904","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}