Pub Date : 2025-06-05DOI: 10.1038/s41422-025-01135-2
Yun Zhu, Tingting Lin, Guoliang Yin, Linhua Tai, Lianwan Chen, Jing Ma, Guoning Huang, Yi Lu, Zhiyong Zhang, Binbin Wang, Suren Chen, Fei Sun
The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2, we resolved the in-cell structure of mouse sperm CA at a subnanometer resolution and built a near-complete atomic model. Our analysis identified 39 CA-associated proteins, including eight previously unreported components. By presenting the full-length structures of CFAP47 and HYDIN, we elucidate their molecular roles in tethering the C1 and C2 microtubules within the CA. Specifically, HYDIN forms a semicircular chain that encircles C1 and C2, with its N-terminal half driving the C1–C2 connection and its C-terminal half providing axial support in C2. CFAP47, the core structural component of the bridge, binds C1 through its N-terminal domains, interacts with HYDIN via its central CFAP47-ring, and anchors to C2 through its C-terminal region. The significantly reduced sperm motility and impaired CA structure observed in Cfap47-knockout mice confirmed the important role of CFAP47. Furthermore, genetic analysis of infertile Chinese men with asthenozoospermia identified previously unreported mutations in the CFAP47. The CA structural model elucidates the pathogenic mechanisms of these mutations, establishing a direct link between CFAP47 dysfunction and impaired sperm motility. Therefore, our study provides mechanistic insights into CA-related fertility disorders.
{"title":"In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia","authors":"Yun Zhu, Tingting Lin, Guoliang Yin, Linhua Tai, Lianwan Chen, Jing Ma, Guoning Huang, Yi Lu, Zhiyong Zhang, Binbin Wang, Suren Chen, Fei Sun","doi":"10.1038/s41422-025-01135-2","DOIUrl":"10.1038/s41422-025-01135-2","url":null,"abstract":"The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2, we resolved the in-cell structure of mouse sperm CA at a subnanometer resolution and built a near-complete atomic model. Our analysis identified 39 CA-associated proteins, including eight previously unreported components. By presenting the full-length structures of CFAP47 and HYDIN, we elucidate their molecular roles in tethering the C1 and C2 microtubules within the CA. Specifically, HYDIN forms a semicircular chain that encircles C1 and C2, with its N-terminal half driving the C1–C2 connection and its C-terminal half providing axial support in C2. CFAP47, the core structural component of the bridge, binds C1 through its N-terminal domains, interacts with HYDIN via its central CFAP47-ring, and anchors to C2 through its C-terminal region. The significantly reduced sperm motility and impaired CA structure observed in Cfap47-knockout mice confirmed the important role of CFAP47. Furthermore, genetic analysis of infertile Chinese men with asthenozoospermia identified previously unreported mutations in the CFAP47. The CA structural model elucidates the pathogenic mechanisms of these mutations, establishing a direct link between CFAP47 dysfunction and impaired sperm motility. Therefore, our study provides mechanistic insights into CA-related fertility disorders.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 8","pages":"551-567"},"PeriodicalIF":25.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233356","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 : 2025-05-29DOI: 10.1038/s41422-025-01133-4
Panagiotis N. Moschou, Peter V. Bozhkov
{"title":"FUSTer than stress granules: a prion-like domain warns plants of heat","authors":"Panagiotis N. Moschou, Peter V. Bozhkov","doi":"10.1038/s41422-025-01133-4","DOIUrl":"10.1038/s41422-025-01133-4","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"473-474"},"PeriodicalIF":25.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01133-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164773","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 : 2025-05-29DOI: 10.1038/s41422-025-01129-0
Sonja Wolff, Susan Erster, Gustavo Palacios, Ute M. Moll
{"title":"Editorial Expression of Concern: p53’s mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity","authors":"Sonja Wolff, Susan Erster, Gustavo Palacios, Ute M. Moll","doi":"10.1038/s41422-025-01129-0","DOIUrl":"10.1038/s41422-025-01129-0","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 8","pages":"614-614"},"PeriodicalIF":25.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172705","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 : 2025-05-16DOI: 10.1038/s41422-025-01127-2
Alina Üffing, Eleanor Attridge, Sharon A. Tooze
{"title":"Targeting an alternative route: autophagy in RAS-driven cancers","authors":"Alina Üffing, Eleanor Attridge, Sharon A. Tooze","doi":"10.1038/s41422-025-01127-2","DOIUrl":"10.1038/s41422-025-01127-2","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"389-390"},"PeriodicalIF":25.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01127-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065802","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 : 2025-05-16DOI: 10.1038/s41422-025-01130-7
Liushuai Li, Yajie Liu, Juhong Rao, Hengrui Hu, Jia Liu, Xi Wang, Jiang Li, Zhihong Hu, Manli Wang
{"title":"Mucin-like protein of Crimean-Congo hemorrhagic fever virus is a key virulence factor and a potent target for developing novel attenuated vaccine","authors":"Liushuai Li, Yajie Liu, Juhong Rao, Hengrui Hu, Jia Liu, Xi Wang, Jiang Li, Zhihong Hu, Manli Wang","doi":"10.1038/s41422-025-01130-7","DOIUrl":"10.1038/s41422-025-01130-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"524-527"},"PeriodicalIF":25.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065801","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 : 2025-05-14DOI: 10.1038/s41422-025-01125-4
Pan Geng, Changxuan Li, Xuebo Quan, Jiaxuan Peng, Zhiying Yao, Yunhe Wang, Ming Yang, Yanning Wang, Yunfan Jin, Yan Xiong, Hongtao Liu, Yijun Qi, Peiguo Yang, Kai Huang, Xiaofeng Fang
The ability to sense cellular temperature and induce physiological changes is pivotal for plants to cope with warming climate. Biomolecular condensation is emerging as a thermo-sensing mechanism, but the underlying molecular basis remains elusive. Here we show that an intrinsically disordered protein FUST1 senses heat via its condensation in Arabidopsis thaliana. Heat-dependent condensation of FUST1 is primarily determined by its prion-like domain (PrLD). All-atom molecular dynamics simulation and experimental validation reveal that PrLD encodes a thermo-switch, experiencing lock-to-open conformational changes that control the intermolecular contacts. FUST1 interacts with integral stress granule (SG) components and localizes in the SGs. Importantly, FUST1 condensation is autonomous and precedes condensation of several known SG markers and is indispensable for SG assembly. Loss of FUST1 significantly delays SG assembly and impairs both basal and acquired heat tolerance. These findings illuminate the molecular basis for thermo-sensing by biomolecular condensation and shed light on the molecular mechanism of heat stress granule assembly.
{"title":"A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis","authors":"Pan Geng, Changxuan Li, Xuebo Quan, Jiaxuan Peng, Zhiying Yao, Yunhe Wang, Ming Yang, Yanning Wang, Yunfan Jin, Yan Xiong, Hongtao Liu, Yijun Qi, Peiguo Yang, Kai Huang, Xiaofeng Fang","doi":"10.1038/s41422-025-01125-4","DOIUrl":"10.1038/s41422-025-01125-4","url":null,"abstract":"The ability to sense cellular temperature and induce physiological changes is pivotal for plants to cope with warming climate. Biomolecular condensation is emerging as a thermo-sensing mechanism, but the underlying molecular basis remains elusive. Here we show that an intrinsically disordered protein FUST1 senses heat via its condensation in Arabidopsis thaliana. Heat-dependent condensation of FUST1 is primarily determined by its prion-like domain (PrLD). All-atom molecular dynamics simulation and experimental validation reveal that PrLD encodes a thermo-switch, experiencing lock-to-open conformational changes that control the intermolecular contacts. FUST1 interacts with integral stress granule (SG) components and localizes in the SGs. Importantly, FUST1 condensation is autonomous and precedes condensation of several known SG markers and is indispensable for SG assembly. Loss of FUST1 significantly delays SG assembly and impairs both basal and acquired heat tolerance. These findings illuminate the molecular basis for thermo-sensing by biomolecular condensation and shed light on the molecular mechanism of heat stress granule assembly.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"483-496"},"PeriodicalIF":25.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01125-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945476","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}
Cytoplasmic DNA emerges as a consequence of genomic instability. However, its potential role in disease diagnosis has yet to be fully explored. Here we analyzed DNA remnants in mature red blood cells (rbcDNA) from both healthy individuals and cancer patients. Our study unveiled distinct genomic profiles in rbcDNA from cancer patients with early-stage solid tumors compared to those of healthy donors. Significant changes in read counts at specific genomic regions within rbcDNA were identified in patients, which were termed tumor-associated rbcDNA features. These features demonstrated potential for highly accurate early-stage cancer detection, proposing a novel approach for cancer detection. Moreover, tumor-associated rbcDNA features were observed in tumor mouse models, with some features being conserved between mice and humans. Chronic, but not transient, up-regulation of interleukin-18 is essential for the development of these features by promoting DNA damage in bone marrow hematopoietic cells through the up-regulation of NR4A1. These results underscore the remote regulation of chromosomal stability in hematopoietic cells by solid tumors and propose tumor-associated rbcDNA features as a promising strategy for early cancer detection.
{"title":"DNA remnants in red blood cells enable early detection of cancer","authors":"Haobo Sun, Xingyun Yao, Yurong Jiao, Xiangxing Kong, Yuehua Han, Ying Li, Jianping Ge, Yanfei Cao, Hongsheng Lu, Pingli Wang, Yu Xu, Jun Li, Kefeng Ding, Xiaofei Gao","doi":"10.1038/s41422-025-01122-7","DOIUrl":"10.1038/s41422-025-01122-7","url":null,"abstract":"Cytoplasmic DNA emerges as a consequence of genomic instability. However, its potential role in disease diagnosis has yet to be fully explored. Here we analyzed DNA remnants in mature red blood cells (rbcDNA) from both healthy individuals and cancer patients. Our study unveiled distinct genomic profiles in rbcDNA from cancer patients with early-stage solid tumors compared to those of healthy donors. Significant changes in read counts at specific genomic regions within rbcDNA were identified in patients, which were termed tumor-associated rbcDNA features. These features demonstrated potential for highly accurate early-stage cancer detection, proposing a novel approach for cancer detection. Moreover, tumor-associated rbcDNA features were observed in tumor mouse models, with some features being conserved between mice and humans. Chronic, but not transient, up-regulation of interleukin-18 is essential for the development of these features by promoting DNA damage in bone marrow hematopoietic cells through the up-regulation of NR4A1. These results underscore the remote regulation of chromosomal stability in hematopoietic cells by solid tumors and propose tumor-associated rbcDNA features as a promising strategy for early cancer detection.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 8","pages":"568-587"},"PeriodicalIF":25.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926856","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}
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