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Autophagic flux blockade under hypocapnia reveals CO2-sensitive regulation of autophagy-lysosome homeostasis. 低碳酸血症下的自噬通量阻断揭示了自噬溶酶体稳态的CO₂敏感调节。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-30 DOI: 10.1242/bio.062414
Naghmana Ashraf, Zhen Sun, Jeanine L Van Nostrand
{"title":"Autophagic flux blockade under hypocapnia reveals CO2-sensitive regulation of autophagy-lysosome homeostasis.","authors":"Naghmana Ashraf, Zhen Sun, Jeanine L Van Nostrand","doi":"10.1242/bio.062414","DOIUrl":"10.1242/bio.062414","url":null,"abstract":"<p><p>Hypocapnia, a reduction in partial pressure of carbon dioxide (CO2), commonly occurs in clinical contexts such as mechanical ventilation, panic disorder, and brain injury, yet its impact on cellular homeostasis remains poorly understood. Given the central role of autophagy in stress adaptation, we investigated how low CO2 influences autophagic flux and lysosomal function. We found that hypocapnia induces autophagosome accumulation while impairing cargo degradation, indicating a blockade in autophagic flux. This response was accompanied by increased lysosome biogenesis but, paradoxically, reduced autophagosome-lysosome fusion and lysosomal proteolytic activity. Mechanistically, hypocapnia promoted TFE3 dephosphorylation and nuclear translocation, driving transcriptional activation of lysosomal genes. Concurrently, suppressed AMPK activity and sustained mTOR signaling revealed a unique metabolic state that uncouples energy stress from canonical autophagy control. As such, inhibition of both mTORC1 and mTORC2 was sufficient to restore autophagic flux. Notably, increased pH was not sufficient to drive this program. These findings identify hypocapnia as a previously unrecognized modulator of autophagy that disrupts autophagosome-lysosome fusion and terminal degradation, positioning CO2 tension as a critical regulator of cellular stress responses.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Cat brains age like humans: translating time shows pet cats live to be natural models for human aging. 猫的大脑像人类一样衰老:《翻译时代》显示,宠物猫是人类衰老的自然模型。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-22 DOI: 10.1242/bio.062604
Capucine Januel, Elijah Morrow, Ryan Gibson, Amanda Gross, Alexandra A de Sousa, Brier A Rigby Dames, Christine J Charvet
{"title":"Cat brains age like humans: translating time shows pet cats live to be natural models for human aging.","authors":"Capucine Januel, Elijah Morrow, Ryan Gibson, Amanda Gross, Alexandra A de Sousa, Brier A Rigby Dames, Christine J Charvet","doi":"10.1242/bio.062604","DOIUrl":"10.1242/bio.062604","url":null,"abstract":"<p><p>Whether an animal can achieve a lifespan equivalent to a human in their 80s remains an open question. Cats may serve as valuable models for human aging because there is some evidence that they can develop human related aging patterns. Here, we leveraged 3754 observations extracted from age-related brain variation, blood chemistry profiles, and other data to equate ages across the lifespan of humans and cats. We used structural MR scans (7T and 3T MRI) from pet and colony cats to quantify age-related brain metrics during aging. Cat and human brains exhibit similar age-related patterns of brain atrophy. We used common patterns of brain change and other health-related metrics to generate age alignments across the lifespan to late stages of life (e.g. an 80-year-old human equates to a 15-year-old cat). We also collected observations across multiple cat populations, including pets, zoos, and colonies to encapsulate individual variation in cross-species age alignments. One major finding to emerge is that pet cats are studied at significantly older ages than colony cats, and pet cats demonstrate a high degree of age-related brain atrophy. We demonstrate that it is feasible to translate ages across the lifespan of humans and cats.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
An open-source high-precision hive for long-term honeybee observation and research. 用于长期观察和研究蜜蜂的开源高精度蜂巢。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-30 DOI: 10.1242/bio.062523
Jiří Ulrich, Martin Stefanec, Tomáš Rouček, Laurenz Alexander Fedotoff, Harald Pascher, Zdeněk Rozsypálek, Thomas Schmickl, Tomáš Krajník
{"title":"An open-source high-precision hive for long-term honeybee observation and research.","authors":"Jiří Ulrich, Martin Stefanec, Tomáš Rouček, Laurenz Alexander Fedotoff, Harald Pascher, Zdeněk Rozsypálek, Thomas Schmickl, Tomáš Krajník","doi":"10.1242/bio.062523","DOIUrl":"10.1242/bio.062523","url":null,"abstract":"<p><p>Honeybees have been of interest due to their important role in ecology and agriculture. Apis mellifera is a uniquely manageable eusocial insect, defined by its self-organising behaviour, extensive history of domestication and indispensable agricultural role. These attributes, alongside recent high annual losses, necessitate continued scientific research. This research is further accelerated by artificial intelligence and computer vision methods that automatically analyse events in observation hives. However, many findings are not reproducible, even though the methods and models are open source. One of the key problems is the lack of standardisation in the observation-hive setup, leading to significantly different image properties. We present an open-hardware setup design that can be adapted to various research needs and further support the repeatability and transferability of experiments. Using an open-source tracking system, we demonstrate the proposed observation hive on the application of focused observation of an individual honeybee. The hardware designs and software codes are publicly available to the community.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Worms About Town: a citizen science project discovers microsporidian parasites of nematodes through environmental sampling. 关于城镇的蠕虫:一个公民科学项目通过环境采样发现线虫的微孢子虫寄生虫。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-08 DOI: 10.1242/bio.062473
Jonathan Tersigni, Edward B James, Aaron W Reinke
{"title":"Worms About Town: a citizen science project discovers microsporidian parasites of nematodes through environmental sampling.","authors":"Jonathan Tersigni, Edward B James, Aaron W Reinke","doi":"10.1242/bio.062473","DOIUrl":"10.1242/bio.062473","url":null,"abstract":"<p><p>Microsporidia are a diverse group of fungal parasites that infect humans and agriculturally important animals. Caenorhabditis elegans has emerged as a powerful host for investigating microsporidian biology, yet how ecological factors such as geography, seasonality, temporality, and sample substrate impact infection of C. elegans and other nematodes remains unclear. To address this, we developed a citizen scientist network, Worms About Town, to annually survey wild nematodes for microsporidia across Toronto, Canada. Here, we describe results from the first year (2024) of the project. One hundred twenty-seven environmental samples from various plant substrates were collected, 60 of which contained wild nematodes and four of which were infected with microsporidia. Two isolates of Nematocida homosporus, a known generalist microsporidian of nematodes, were identified. The other two microsporidia isolates belong to undescribed species of Pancytospora and Enteropsectra, genera distantly related to human-infecting microsporidia. Three nematode isolates of the Caenorhabditis genus were discovered, including two isolates of C. elegans, a species not previously reported in Ontario. Both N. homosporus isolates were found in C. elegans, and one can infect a laboratory strain of C. elegans. Our study expands knowledge of natural nematode-microsporidia diversity and provides a framework for systematically investigating how ecological factors shape this host-parasite system.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis. GATA4及其靶基因TBX2在人类心脏发生调控中的保守作用。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 DOI: 10.1242/bio.062553
Nicola Graham, Pavel Kirilenko, Ilya Patrushev, Ewan D Fowler, Peter Kille, Michael Gilchrist, Nick D L Owens, Branko Latinkic
{"title":"Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis.","authors":"Nicola Graham, Pavel Kirilenko, Ilya Patrushev, Ewan D Fowler, Peter Kille, Michael Gilchrist, Nick D L Owens, Branko Latinkic","doi":"10.1242/bio.062553","DOIUrl":"10.1242/bio.062553","url":null,"abstract":"<p><p>The transcription factor GATA4 is a key mediator of cardiogenesis, regulating this process through the expression of downstream target genes, only a subset of which have been identified. Using a gain-of-function model based on pluripotent ectoderm explants from Xenopus embryos expressing GATA4, we identified a set of GATA4 targets that are also regulated by cardiogenic Nodal signalling. GATA4 was shown to be required for the expression of the target genes tbx2 and prdm1, both of which were subsequently found to have roles of their own in vivo, as downregulation of tbx2, a positive target, and overexpression of prdm1, a negative target, interferes with cardiac development in Xenopus embryos. The conservation of the GATA4-TBX2-PRDM1 regulatory relationship was demonstrated in human induced pluripotent stem cell-derived cardiomyocytes. Loss of GATA4 function resulted in downregulation of TBX2, upregulation of PRDM1 and failure of cardiogenesis. GATA4-deficient cells failed to form normal cardiomyocytes, with most cells adopting alternative fates and only a small minority displaying an aberrant cardiomyocyte phenotype. Genome-wide transcriptomic analysis documented a marked reduction in cardiomyocyte and endothelial cell transcriptomes, accompanied by upregulation of transcriptional profiles associated with smooth muscle cells and fibroblasts. Disruption of TBX2 led to the formation of cardiomyocytes with hypertrophic-like features consistent with maladaptive remodelling. In addition, although PRDM1 was not essential for cardiomyocyte formation, it appeared to play a role in fine-tuning the timing and levels of gene expression. Together, these findings establish a conserved regulatory relationship between GATA4 and its target genes TBX2 and PRDM1 and suggest important roles for these factors in modulating cardiomyocyte development.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
SPSP-1 is a sperm protein required for C. elegans hermaphrodite sperm production and embryogenesis. SPSP-1是秀丽隐杆线虫雌雄同体精子产生和胚胎发生所必需的精子蛋白。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-30 DOI: 10.1242/bio.062634
Darline Murat, Margaret Nagorski, Ji Kent Kwah, Shannon Pfeiffer, Nancy Duker, Frank Döring, Aimee Jaramillo-Lambert
{"title":"SPSP-1 is a sperm protein required for C. elegans hermaphrodite sperm production and embryogenesis.","authors":"Darline Murat, Margaret Nagorski, Ji Kent Kwah, Shannon Pfeiffer, Nancy Duker, Frank Döring, Aimee Jaramillo-Lambert","doi":"10.1242/bio.062634","DOIUrl":"10.1242/bio.062634","url":null,"abstract":"<p><p>Development requires the fusion of two gametes each with a haploid complement of DNA and the necessary components (RNA, proteins, organelles) needed for early cellular processes and divisions. The C. elegans paternal-effect embryonic lethal gene, spe-11, is one of the few known sperm components required for normal development. Sperm-provided SPE-11 forms a complex with the oocyte protein OOPS-1 at fertilization that mediates egg activation events. In this manuscript, we identified SPSP-1, a sperm protein that is associated with SPE-11. We found that SPSP-1 co-localizes with SPE-11 during spermatogenesis and in spermatids. SPSP-1 does not appear to play a role in egg activation like SPE-11. However, SPSP-1 is required to produce normal levels of hermaphrodite sperm and for wild-type levels of embryonic viability.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Post-ejaculatory thermal sensitivity of sperm performance in the high-altitude lizard Phymaturus extrilidus. 高原蜥蜴精后表现的热敏性。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-06-15 Epub Date: 2026-06-30 DOI: 10.1242/bio.062678
Rodrigo Gómez Alés, Guadalupe López Juri, Franco Valdez Ovallez, Maximiliano Tourmente
{"title":"Post-ejaculatory thermal sensitivity of sperm performance in the high-altitude lizard Phymaturus extrilidus.","authors":"Rodrigo Gómez Alés, Guadalupe López Juri, Franco Valdez Ovallez, Maximiliano Tourmente","doi":"10.1242/bio.062678","DOIUrl":"10.1242/bio.062678","url":null,"abstract":"<p><p>Rising environmental temperatures may differentially affect physiological processes in ectotherms, with sperm function representing a potentially critical but understudied vulnerability. We experimentally evaluated post-ejaculatory thermal sensitivity of sperm kinematics in the high-altitude viviparous lizard Phymaturus extrilidus. Ejaculated sperm from adult males were exposed to three ecologically relevant temperatures (28°C, 35°C, and 38°C), and motility and swimming parameters were quantified over a 2-h incubation period using computer-assisted sperm analysis. Sperm performance was strongly affected by temperature, incubation time, and their interaction, indicating progressive thermal damage. Contrary to our prediction, peak sperm motility and swimming performance occurred at 28°C rather than at the preferred body temperature (35°C). Incubation at 35°C and especially 38°C caused marked, declines in motility, curvilinear velocity (VCL), and average path velocity (VAP), while straight-line velocity (VSL) remained comparatively stable. Increased linearity and straightness at elevated temperatures suggest reduced trajectory complexity and flagellar oscillation amplitude. These results reveal a mismatch between the thermal optimum for sperm function and locomotor performance, highlighting a physiological trade-off between somatic and reproductive traits. Under climate-warming scenarios, reduced access to cooler microhabitats may accelerate sperm senescence and compromise reproductive success in high-mountain ectotherms.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Meeting Review of the Cryospheric Ecosystems Conference, 1-4 September 2025, Poznań, Poland. 冰冻圈生态系统会议综述,2025年9月1日至4日,波兰波兹纳斯。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-05-15 Epub Date: 2026-05-11 DOI: 10.1242/bio.062385
Kinga Skoczeń, Zofia Kujawa, Magdalena Strawa, Filip Marcinkowski, Selina Tinkhauser, Mikołaj Jastrzębski, Róża Ulikowska
{"title":"Meeting Review of the Cryospheric Ecosystems Conference, 1-4 September 2025, Poznań, Poland.","authors":"Kinga Skoczeń, Zofia Kujawa, Magdalena Strawa, Filip Marcinkowski, Selina Tinkhauser, Mikołaj Jastrzębski, Róża Ulikowska","doi":"10.1242/bio.062385","DOIUrl":"10.1242/bio.062385","url":null,"abstract":"<p><p>The Cryospheric Ecosystems Conference, held at Adam Mickiewicz University in Poznań from September 1 to 4, 2025, brought together 80 scientists, researchers, and students from 15 countries. The conference was held as part of the International Year of Glaciers' Preservation 2025, providing the ideal context and platform for sharing the results and discussions on recent discoveries, emerging threats, the latest techniques, and future projects. The conference highlighted the importance of cryospheric environments, such as ice sheets, glaciers and snow, which host unique biodiversity. The event covered the cascading effects of global warming on glacier retreat and biodiversity, the role of phototrophs in snow and ice, the biogeochemical cycling of fundamental elements such as carbon, nitrogen and phosphorus, and pollutants in cryospheric environments. Here we present the key outcomes and discussions of the conference, emphasizing the importance of cryospheric ecosystems monitoring and protection.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Glucocorticoids intrinsically redirect naïve CD4+ T cells to the bone marrow for preservation in malnourished mice. 糖皮质激素本质上重定向naïve CD4+ T细胞到骨髓保存在营养不良的小鼠。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-05-15 Epub Date: 2026-05-12 DOI: 10.1242/bio.062485
Madeline L Smith, Jacob Hanes, Takesha R Foster, Clay Phillips, Kwesi A Dadzie, Melanie R Gubbels Bupp
{"title":"Glucocorticoids intrinsically redirect naïve CD4+ T cells to the bone marrow for preservation in malnourished mice.","authors":"Madeline L Smith, Jacob Hanes, Takesha R Foster, Clay Phillips, Kwesi A Dadzie, Melanie R Gubbels Bupp","doi":"10.1242/bio.062485","DOIUrl":"10.1242/bio.062485","url":null,"abstract":"<p><p>Malnutrition impairs immunity and contributes significantly to child mortality. Among other immune changes during malnutrition, effector T cells experience a decline in number and function. As little is known about the effect of malnutrition on naïve T cells, we examined the impact of malnutrition on the naïve T-cell population. During malnutrition, the number of naïve T cells decreased in the lymph nodes and increased in the bone marrow, where naïve CD4+ T cells experienced less apoptosis than controls. An adoptive transfer experiment revealed that malnourished naïve CD4+ T cells preferentially migrated to the bone marrow, while ad libitum-fed control cells preferentially migrated to the lymph nodes in a T-cell-intrinsic fashion. Additionally, T-cell-specific lack of the glucocorticoid receptor greatly reduced the number of naïve T cells in the bone marrow of malnourished mice, while dexamethasone treatment elevated the number of naïve CD4+ T cells in the bone marrow. T-cell sensitivity to glucocorticoids was required for elevated expression of CXCR4 and CCR7 in naïve CD4+ T cells during malnutrition. Overall, naïve CD4+ T-cell migration to the bone marrow during malnutrition is intrinsic, requires sensitivity to glucocorticoids, and likely contributes to naïve T-cell preservation in mice.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Kinetic properties of optogenetic site-specific DNA recombination by LiCre-loxP. LiCre-loxP光遗传位点特异性DNA重组的动力学性质。
IF 1.8 4区 生物学
Biology Open Pub Date : 2026-05-15 Epub Date: 2026-05-14 DOI: 10.1242/bio.062381
Alice Dufour, Hélène Duplus-Bottin, Thomas Boukéké-Lesplulier, Eliane Casassa, Gérard Triqueneaux, Léo Tarbouriech, Camille Darthenay-Kiennemann, Agnès Dumont, Catherine Moali, Franck Vittoz, Daniel Jost, Gaël Yvert
{"title":"Kinetic properties of optogenetic site-specific DNA recombination by LiCre-loxP.","authors":"Alice Dufour, Hélène Duplus-Bottin, Thomas Boukéké-Lesplulier, Eliane Casassa, Gérard Triqueneaux, Léo Tarbouriech, Camille Darthenay-Kiennemann, Agnès Dumont, Catherine Moali, Franck Vittoz, Daniel Jost, Gaël Yvert","doi":"10.1242/bio.062381","DOIUrl":"10.1242/bio.062381","url":null,"abstract":"<p><p>Advances in optogenetics now allow specific modifications to the DNA of live cells with light. However, successfully using these technologies requires knowing their properties in terms of sensitivity, efficiency, kinetics and mechanism. We previously developed an optogenetic tool made of a single chimeric protein called LiCre that enables the induction of specific changes in the genome with blue light via DNA recombination between loxP sites ( Duplus-Bottin et al., 2021). Here, we used in vitro and in vivo experiments combined with kinetic modeling to provide a deeper characterization of the photoactivated LiCre-loxP recombination reaction. We find that LiCre binds DNA with high affinity in the absence of a light stimulus and that this binding is cooperative, although not as much as for the Cre recombinase from which LiCre was derived. In yeast, the addition of riboflavin to the culture medium had no effect on LiCre's efficiency, even when cells over-expressed riboflavin kinase, suggesting that the abundance of the flavin mononucleotide cofactor is not limiting for the reaction. However, LiCre's efficiency in yeast gradually increased when raising the temperature from 20°C to 37°C. The recombination kinetics observed in live cells are best explained by a model where the photoactivation of two or more DNA-bound LiCre units (happening in seconds) can produce (in several minutes) a functional recombination synapse. This model was able to capture the effect of a point mutation altering LiCre's light cycle. This deeper understanding of the LiCre-loxP system provides additional knowledge for designing experiments where specific genetic changes are induced in live cells with light.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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