Cell Discovery最新文献_第4页

Multiple infections with Omicron variants increase breadth and potency of Omicron-specific neutralizing antibodies. 多次感染奥米克隆变异增加了奥米克隆特异性中和抗体的广度和效力。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-20 DOI: 10.1038/s41421-025-00800-5

Lei You, Luning Zhang, Shengqun Ouyang, Bo Gao, Yanan Li, Jialu Li, Ningbo Wu, Hong Wang, Shiqi Sun, Jinfeng Li, Zi Yin, Ziyang Xu, Yao Chen, Yiwen Zhu, Shuangyan Zhang, Zhan Xu, Tianyu Zhang, Zhaoyuan Liu, Chuanxin Huang, Bin Li, Jieming Qu, Bing Su, Leng-Siew Yeap

{"title":"Multiple infections with Omicron variants increase breadth and potency of Omicron-specific neutralizing antibodies.","authors":"Lei You, Luning Zhang, Shengqun Ouyang, Bo Gao, Yanan Li, Jialu Li, Ningbo Wu, Hong Wang, Shiqi Sun, Jinfeng Li, Zi Yin, Ziyang Xu, Yao Chen, Yiwen Zhu, Shuangyan Zhang, Zhan Xu, Tianyu Zhang, Zhaoyuan Liu, Chuanxin Huang, Bin Li, Jieming Qu, Bing Su, Leng-Siew Yeap","doi":"10.1038/s41421-025-00800-5","DOIUrl":"10.1038/s41421-025-00800-5","url":null,"abstract":"Despite high vaccination rates, highly evolved Omicron variants have caused widespread infections and, in some cases, recurrent infections in the human population. As the population continues to be threatened by new variants, it is critical to understand how the dynamic cross-reactive antibody response evolves and affects protection. Here, we longitudinally profiled neutralizing antibodies in individuals who experienced three Omicron waves in China over an 18-month period following the lifting of the COVID restriction. We found that individuals with BA.5/BF.7 and XBB dual infections had increased breadth and neutralizing potency of Omicron-specific antibodies compared to those with a BA.5/BF.7 single infection, and were thus more resistant to JN.1/XDV.1 infection in the third wave. During the second infection, a new imprint based on the previously infected variant was established, and the antibodies developed high cross-reactivity against the Omicron variants and less against vaccine-derived WT SARS-CoV-2. Our results suggest that the high titer and breadth of cross-reactive antibodies from multiple infections may be protective against future infection with Omicron variants such as JN.1, but may still be vulnerable to antigenically advanced subvariants such as KP.3.1.1 and XEC.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"49"},"PeriodicalIF":13.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101504","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}

引用次数: 0

Spatiotemporal 3D chromatin organization across multiple brain regions during human fetal development. 人类胎儿发育过程中多个脑区的时空三维染色质组织。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-16 DOI: 10.1038/s41421-025-00798-w

Yaoyu Sun, Min Li, Chao Ning, Lei Gao, Zhenbo Liu, Suijuan Zhong, Junjie Lv, Yuwen Ke, Xinxin Wang, Qiang Ma, Zeyuan Liu, Shuaishuai Wu, Hao Yu, Fangqi Zhao, Jun Zhang, Qian Gong, Jiang Liu, Qian Wu, Xiaoqun Wang, Xuepeng Chen

{"title":"Spatiotemporal 3D chromatin organization across multiple brain regions during human fetal development.","authors":"Yaoyu Sun, Min Li, Chao Ning, Lei Gao, Zhenbo Liu, Suijuan Zhong, Junjie Lv, Yuwen Ke, Xinxin Wang, Qiang Ma, Zeyuan Liu, Shuaishuai Wu, Hao Yu, Fangqi Zhao, Jun Zhang, Qian Gong, Jiang Liu, Qian Wu, Xiaoqun Wang, Xuepeng Chen","doi":"10.1038/s41421-025-00798-w","DOIUrl":"10.1038/s41421-025-00798-w","url":null,"abstract":"Elucidating the regulatory mechanisms underlying the development of different brain regions in humans is essential for understanding advanced cognition and neuropsychiatric disorders. However, the spatiotemporal organization of three-dimensional (3D) chromatin structure and its regulatory functions across different brain regions remain poorly understood. Here, we generated an atlas of high-resolution 3D chromatin structure across six developing human brain regions, including the prefrontal cortex (PFC), primary visual cortex (V1), cerebellum (CB), subcortical corpus striatum (CS), thalamus (TL), and hippocampus (HP), spanning gestational weeks 11-26. We found that the spatial and temporal dynamics of 3D chromatin organization play a key role in regulating brain region development. We also identified H3K27ac-marked super-enhancers as key contributors to shaping brain region-specific 3D chromatin structures and gene expression patterns. Finally, we uncovered hundreds of neuropsychiatric GWAS SNP-linked genes, shedding light on critical molecules in various neuropsychiatric disorders. In summary, our findings provide important insights into the 3D chromatin regulatory mechanisms governing brain region-specific development and can serve as a valuable resource for advancing our understanding of neuropsychiatric disorders.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"50"},"PeriodicalIF":13.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076222","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}

引用次数: 0

Structural insight into the self-activation and G-protein coupling of P2Y2 receptor. P2Y2受体自激活和g蛋白偶联的结构研究。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-13 DOI: 10.1038/s41421-025-00797-x

Baoliang Lan, Shuhao Zhang, Kai Chen, Shengjie Dai, Jiaqi Fei, Kaixuan Gao, Xiaoou Sun, Bin Lin, Xiangyu Liu

{"title":"Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.","authors":"Baoliang Lan, Shuhao Zhang, Kai Chen, Shengjie Dai, Jiaqi Fei, Kaixuan Gao, Xiaoou Sun, Bin Lin, Xiangyu Liu","doi":"10.1038/s41421-025-00797-x","DOIUrl":"10.1038/s41421-025-00797-x","url":null,"abstract":"Purinergic P2Y2 receptor (P2Y2R) represents a typically extracellular ATP and UTP sensor for mediating purinergic signaling. Despite its importance as a pharmacological target, the molecular mechanisms underlying ligand recognition and G-protein coupling have remained elusive due to lack of structural information. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of the apo P2Y2R in complex with Gq, ATP-bound P2Y2R in complex with Gq or Go, and UTP-bound P2Y4R in complex with Gq. These structures reveal the similarities and distinctions of ligand recognition within the P2Y receptor family. Furthermore, a comprehensive analysis of G-protein coupling reveals that P2Y2R exhibits promiscuity in coupling with both Gq and Go proteins. Combining molecular dynamics simulations and signaling assays, we elucidate the molecular mechanisms by which P2Y2R differentiates pathway-specific Gq or Go coupling through distinct structural components on the intracellular side. Strikingly, we identify a helix-like segment within the N-terminus that occupies the orthosteric ligand-binding pocket of P2Y2R, accounting for its self-activation. Taken together, these findings provide a molecular framework for understanding the activation mechanism of P2Y2R, encompassing ligand recognition, G-protein coupling, and a novel N-terminus-mediated self-activation mechanism.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"47"},"PeriodicalIF":13.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984868","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}

引用次数: 0

Structural insights into ligand recognition and activation of human purinergic receptor P2Y14. 人嘌呤能受体P2Y14配体识别和激活的结构见解。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-13 DOI: 10.1038/s41421-025-00799-9

Quanchang Gu, Zhenyu Lv, Tianxin Wang, Wenqin Tang, Xuzhen Guo, Xiangling Huang, Fahui Li, Jiangyun Wang

引用次数: 0

Psychological stress-induced systemic corticosterone directly sabotages intestinal stem cells and exacerbates colitis. 心理应激诱导的全身皮质酮直接破坏肠道干细胞，加重结肠炎。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-13 DOI: 10.1038/s41421-025-00796-y

Xiaole Sheng, Lanfei Jin, Zhengrong Yao, Jiaji Gu, Longtao Zhu, Andi Huang, Junxuan Peng, Xin Xu, Xiaolong Ge, Wei Zhou, Jinghao Sheng, Zhengping Xu, Rongpan Bai

{"title":"Psychological stress-induced systemic corticosterone directly sabotages intestinal stem cells and exacerbates colitis.","authors":"Xiaole Sheng, Lanfei Jin, Zhengrong Yao, Jiaji Gu, Longtao Zhu, Andi Huang, Junxuan Peng, Xin Xu, Xiaolong Ge, Wei Zhou, Jinghao Sheng, Zhengping Xu, Rongpan Bai","doi":"10.1038/s41421-025-00796-y","DOIUrl":"10.1038/s41421-025-00796-y","url":null,"abstract":"Psychological stress has profound impacts on the gastrointestinal tract via the brain‒gut axis. However, its effects on intestinal stem cells (ISCs) and the resulting implication for intestinal homeostasis remain poorly understood. Here, we observed a notable reduction in both the quantity and proliferative capacity of ISCs under chronic stress conditions, driven by elevated levels of corticosterone resulting from activation of the hypothalamic‒pituitary‒adrenal (HPA) axis. Mechanistically, corticosterone directly interacts with its receptor, nuclear receptor subfamily 3 group c member 1 (NR3C1), leading to increased expression of FKBP prolyl isomerase 5 (FKBP5) in ISCs. Subsequently, FKBP5 negatively regulates AKT activation by facilitating its dephosphorylation at Ser473, ultimately enhancing nuclear translocation of forkhead box O (FoxO) and inhibiting ISC proliferative activity. Consequently, ISC dysfunction contributes to the stress-driven exacerbation of DSS-induced colitis. Collectively, these findings reveal an intrinsic brain-to-gut regulatory pathway whereby psychological stress impairs ISC activity via corticosterone elevation, providing a mechanistic explanation for stress-enhanced susceptibility to colitis.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"46"},"PeriodicalIF":13.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962449","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}

引用次数: 0

Distinct methylomic signatures of high-altitude acclimatization and adaptation in the Tibetan Plateau. 青藏高原高海拔环境适应的不同甲基组特征。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-06 DOI: 10.1038/s41421-025-00795-z

Feifei Cheng, Ren-Juan Shen, Zhili Zheng, Zhen Ji Chen, Peng-Juan Huang, Zhuo-Kun Feng, Xiaoman Li, Na Lin, Meiqin Zheng, Yuanbo Liang, Jia Qu, Fan Lu, Zi-Bing Jin, Jian Yang

{"title":"Distinct methylomic signatures of high-altitude acclimatization and adaptation in the Tibetan Plateau.","authors":"Feifei Cheng, Ren-Juan Shen, Zhili Zheng, Zhen Ji Chen, Peng-Juan Huang, Zhuo-Kun Feng, Xiaoman Li, Na Lin, Meiqin Zheng, Yuanbo Liang, Jia Qu, Fan Lu, Zi-Bing Jin, Jian Yang","doi":"10.1038/s41421-025-00795-z","DOIUrl":"https://doi.org/10.1038/s41421-025-00795-z","url":null,"abstract":"High altitude presents a challenging environment for human settlement. DNA methylation is an essential epigenetic mechanism that responds to environmental stimuli, but its roles in high-altitude short-term acclimatization (STA) and long-term adaptation (LTA) are poorly understood. Here, we conducted a methylome-wide association study involving 687 native highlanders and 299 acclimatized newcomers in the Tibetan Plateau and 462 native lowlanders to identify differentially methylated sites (DMSs) associated with STA or LTA. We identified 93 and 4070 DMSs for STA and LTA, respectively, which had no overlap, showed opposite asymmetric effect size patterns, and resided near genes enriched in distinct biological pathways/processes (e.g., cell cycle for STA and immune diseases and calcium signalling pathway for LTA). Epigenetic clock analysis revealed evidence of accelerated ageing in the acclimatized newcomers compared to the native lowlanders. Our research provides novel insights into epigenetic regulation in relation to high altitude and intervention strategies for altitude-related ageing or illnesses.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"45"},"PeriodicalIF":13.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980584","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}

引用次数: 0

A basigin antibody modulates MCTs to impact tumor metabolism and immunity. 一种基底蛋白抗体调节mct影响肿瘤代谢和免疫。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-06 DOI: 10.1038/s41421-025-00777-1

Heng Zhang, Xuemei Yang, Yue Xue, Yi Huang, Yingxi Mo, Yurun Huang, Hong Zhang, Xiaofei Zhang, Weixin Zhao, Bin Jia, Ningning Li, Ning Gao, Yue Yang, Dongxi Xiang, Shan Wang, Yi Qin Gao, Jun Liao

{"title":"A basigin antibody modulates MCTs to impact tumor metabolism and immunity.","authors":"Heng Zhang, Xuemei Yang, Yue Xue, Yi Huang, Yingxi Mo, Yurun Huang, Hong Zhang, Xiaofei Zhang, Weixin Zhao, Bin Jia, Ningning Li, Ning Gao, Yue Yang, Dongxi Xiang, Shan Wang, Yi Qin Gao, Jun Liao","doi":"10.1038/s41421-025-00777-1","DOIUrl":"https://doi.org/10.1038/s41421-025-00777-1","url":null,"abstract":"Lactate metabolism and signaling intricately intertwine in the context of cancer and immunity. Basigin, working alongside monocarboxylate transporters MCT1 and MCT4, orchestrates the movement of lactate across cell membranes. Despite their potential in treating formidable tumors, the mechanisms by which basigin antibodies affect basigin and MCTs remain unclear. Our research demonstrated that basigin positively modulates MCT activity. We subsequently developed a basigin antibody that converts basigin into a negative modulator, thereby suppressing lactate transport and enhancing anti-tumor immunity. Additionally, the antibody alters metabolic profiles in NSCLC-PDOs and T cells. Cryo-EM structural analysis and molecular dynamics simulations reveal that the extracellular Ig2 domain and transmembrane domain of basigin regulate MCT1 activity through an allosteric mechanism. The antibody decreases MCT1 transition rate by reducing the flexibility of basigin's Ig2 domain and diminishing interactions between basigin's transmembrane domain and MCT1. These findings underscore the promise of basigin antibodies in combating tumors by modulating metabolism and immunity, and the value of a common therapeutic subunit shared by multiple transporter targets.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"44"},"PeriodicalIF":13.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977614","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}

引用次数: 0

Transport and inhibition mechanisms of human creatine transporter. 人肌酸转运蛋白的转运及抑制机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-05 DOI: 10.1038/s41421-025-00801-4

Jiahui Chen, Yimin Zhang, Nanhao Chen, Jingpeng Ge, Jie Yu

引用次数: 0

Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease. 半胱天冬酶：在细胞死亡、先天免疫和疾病中的结构和分子机制和功能。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-05-05 DOI: 10.1038/s41421-025-00791-3

Eswar Kumar Nadendla, Rebecca E Tweedell, Gary Kasof, Thirumala-Devi Kanneganti

{"title":"Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease.","authors":"Eswar Kumar Nadendla, Rebecca E Tweedell, Gary Kasof, Thirumala-Devi Kanneganti","doi":"10.1038/s41421-025-00791-3","DOIUrl":"https://doi.org/10.1038/s41421-025-00791-3","url":null,"abstract":"Caspases are critical regulators of cell death, development, innate immunity, host defense, and disease. Upon detection of pathogens, damage-associated molecular patterns, cytokines, or other homeostatic disruptions, innate immune sensors, such as NLRs, activate caspases to initiate distinct regulated cell death pathways, including non-lytic (apoptosis) and innate immune lytic (pyroptosis and PANoptosis) pathways. These cell death pathways are driven by specific caspases and distinguished by their unique molecular mechanisms, supramolecular complexes, and enzymatic properties. Traditionally, caspases are classified as either apoptotic (caspase-2, -3, -6, -7, -8, -9, and -10) or inflammatory (caspase-1, -4, -5, and -11). However, extensive data from the past decades have shown that apoptotic caspases can also drive lytic inflammatory cell death downstream of innate immune sensing and inflammatory responses, such as in the case of caspase-3, -6, -7, and -8. Therefore, more inclusive classification systems based on function, substrate specificity, or the presence of pro-domains have been proposed to better reflect the multifaceted roles of caspases. In this review, we categorize caspases into CARD-, DED-, and short/no pro-domain-containing groups and examine their critical functions in innate immunity and cell death, along with their structural and molecular mechanisms, including active site/exosite properties and substrates. Additionally, we highlight the emerging roles of caspases in cellular homeostasis and therapeutic targeting. Given the clinical relevance of caspases across multiple diseases, improved understanding of these proteins and their structure-function relationships is critical for developing effective treatment strategies.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"42"},"PeriodicalIF":13.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968960","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}

引用次数: 0

The assembly of RAB22A/TMEM33/RTN4 initiates a secretory ER-phagy pathway. RAB22A/TMEM33/RTN4的组装启动了分泌性er吞噬途径。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-04-29 DOI: 10.1038/s41421-025-00792-2

Xueping Zheng, Dongmei Fang, Hao Shan, Beibei Xiao, Denghui Wei, Yingyi Ouyang, Lanqing Huo, Zhonghan Zhang, Yuanzhong Wu, Ruhua Zhang, Tiebang Kang, Ying Gao

{"title":"The assembly of RAB22A/TMEM33/RTN4 initiates a secretory ER-phagy pathway.","authors":"Xueping Zheng, Dongmei Fang, Hao Shan, Beibei Xiao, Denghui Wei, Yingyi Ouyang, Lanqing Huo, Zhonghan Zhang, Yuanzhong Wu, Ruhua Zhang, Tiebang Kang, Ying Gao","doi":"10.1038/s41421-025-00792-2","DOIUrl":"https://doi.org/10.1038/s41421-025-00792-2","url":null,"abstract":"Rafeesome, a newly identified multivesicular body (MVB)-like organelle, forms through the fusion of RAB22A-mediated ER-derived noncanonical autophagosomes with RAB22A-positive early endosomes. However, the mechanism underlying the formation of RAB22A-mediated noncanonical autophagosomes remains unclear. Herein, we report a secretory ER-phagy pathway in which the assembly of RAB22A/TMEM33/RTN4 induces the clustering of high-molecular-weight RTN4 oligomers, leading to ER membrane remodeling. This remodeling drives the biogenesis of ER-derived RTN4-positive noncanonical autophagosomes, which are ultimately secreted as TMEM33-marked RAB22A-induced extracellular vesicles (R-EVs) via Rafeesome. Specifically, RAB22A interacts with the tubular ER membrane protein TMEM33, which binds to the TM2 domain of the ER-shaping protein RTN4, promoting RTN4 homo-oligomerization and thereby generating RTN4-enriched microdomains. Consequently, the RTN4 microdomains may induce high curvature of the ER, facilitating the bud scission of RTN4-positive vesicles. These vesicles are transported by ATG9A and develop into isolation membranes (IMs), which are then anchored by LC3-II, a process catalyzed by the ATG12-ATG5-ATG16L1 complex, allowing them to grow into sealed RTN4 noncanonical autophagosome. While being packaged into these ER-derived intermediate compartments, ER cargoes bypass lysosomal degradation and are directed to secretory autophagy via the Rafeesome-R-EV route. Our findings reveal a secretory ER-phagy pathway initiated by the assembly of RAB22A/TMEM33/RTN4, providing new insights into the connection between ER-phagy and extracellular vesicles.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"41"},"PeriodicalIF":13.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968969","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}

引用次数: 0