Cell Discovery最新文献

{"title":"Structural basis of connexin-36 gap junction channel inhibition.","authors":"Xinyue Ding, Simone Aureli, Anand Vaithia, Pia Lavriha, Dina Schuster, Basavraj Khanppnavar, Xiaodan Li, Thorsten B Blum, Paola Picotti, Francesco L Gervasio, Volodymyr M Korkhov","doi":"10.1038/s41421-024-00691-y","DOIUrl":"10.1038/s41421-024-00691-y","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"68"},"PeriodicalIF":13.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417913","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}

{"title":"Clathrin mediates membrane fission and budding by constricting membrane pores.","authors":"Lisi Wei, Xiaoli Guo, Ehud Haimov, Kazuki Obashi, Sung Hoon Lee, Wonchul Shin, Min Sun, Chung Yu Chan, Jiansong Sheng, Zhen Zhang, Ammar Mohseni, Sudhriti Ghosh Dastidar, Xin-Sheng Wu, Xin Wang, Sue Han, Gianvito Arpino, Bo Shi, Maryam Molakarimi, Jessica Matthias, Christian A Wurm, Lin Gan, Justin W Taraska, Michael M Kozlov, Ling-Gang Wu","doi":"10.1038/s41421-024-00677-w","DOIUrl":"10.1038/s41421-024-00677-w","url":null,"abstract":"<p><p>Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"62"},"PeriodicalIF":33.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305464","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}

{"title":"Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma.","authors":"Hanhan Shi, Hao Tian, Tianyu Zhu, Qili Liao, Chang Liu, Peng Yuan, Yongyun Li, Jie Yang, Chunyan Zong, Shichong Jia, Jing Ruan, Shengfang Ge, Renbing Jia, Peiwei Chai, Shiqiong Xu, Xianqun Fan","doi":"10.1038/s41421-024-00683-y","DOIUrl":"10.1038/s41421-024-00683-y","url":null,"abstract":"<p><p>Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8⁺ T cells and an increase in the proportion of naive CD8⁺ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"63"},"PeriodicalIF":33.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305465","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}

{"title":"Author Correction: A genetically encoded ratiometric indicator for tryptophan.","authors":"Rongkun Tao, Kui Wang, Tian-Lun Chen, Xin-Xin Zhang, Jian-Bin Cao, Wen-Quan Zhao, Jiu-Lin Du, Yu Mu","doi":"10.1038/s41421-024-00695-8","DOIUrl":"10.1038/s41421-024-00695-8","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"65"},"PeriodicalIF":33.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300092","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}

{"title":"Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor.","authors":"Sanshan Jin, Shimeng Guo, Youwei Xu, Xin Li, Canrong Wu, Xinheng He, Benxun Pan, Wenwen Xin, Heng Zhang, Wen Hu, Yuling Yin, Tianwei Zhang, Kai Wu, Qingning Yuan, H Eric Xu, Xin Xie, Yi Jiang","doi":"10.1038/s41421-024-00670-3","DOIUrl":"10.1038/s41421-024-00670-3","url":null,"abstract":"<p><p>The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the G_q-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"58"},"PeriodicalIF":33.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236269","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}

{"title":"Leptin receptor neurons in the ventral premammillary nucleus modulate emotion-induced insomnia.","authors":"Xiang-Shan Yuan, Zhe Xiang, Jian-Bo Jiang, Fang Yuan, Mu-Tian Zhang, Kai-Ying Zhang, Zhao-Yi Chen, Wei-Min Qu, Wen-Sheng Li, Zhi-Li Huang","doi":"10.1038/s41421-024-00676-x","DOIUrl":"10.1038/s41421-024-00676-x","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"59"},"PeriodicalIF":33.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236268","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}

{"title":"Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue.","authors":"Saumya Kumar, Afonso P Basto, Filipa Ribeiro, Silvia C P Almeida, Patricia Campos, Carina Peres, Nadia Pulvirenti, Sarwah Al-Khalidi, Anna Kilbey, Jimena Tosello, Eliane Piaggio, Momtchilo Russo, Margarida Gama-Carvalho, Seth B Coffelt, Ed W Roberts, Jens Geginat, Helena F Florindo, Luis Graca","doi":"10.1038/s41421-024-00681-0","DOIUrl":"10.1038/s41421-024-00681-0","url":null,"abstract":"<p><p>Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 cells have been associated with the polarization of humoral responses. However, T follicular helper cells (Tfh) have a unique ability to access the B cell follicle and support the germinal center (GC) responses by providing B cell help. We investigated the specialization of Tfh cells induced under type-1 and type-2 conditions. We first studied homogenous Tfh cell populations generated by adoptively transferred TCR-transgenic T cells in mice immunized with type-1 and type-2 adjuvants. Using a machine learning approach, we established a gene expression signature that discriminates Tfh cells polarized towards type-1 and type-2 response, defined as Tfh1 and Tfh2 cells. The distinct signatures of Tfh1 and Tfh2 cells were validated against datasets of Tfh cells induced following lymphocytic choriomeningitis virus (LCMV) or helminth infection. We generated single-cell and spatial transcriptomics datasets to dissect the heterogeneity of Tfh cells and their localization under the two immunizing conditions. Besides a distinct specialization of GC Tfh cells under the two immunizations and in different regions of the lymph nodes, we found a population of Gzmk⁺ Tfh cells specific for type-1 conditions. In human individuals, we could equally identify CMV-specific Tfh cells that expressed Gzmk. Our results show that Tfh cells acquire a specialized function under distinct types of immune responses and with particular properties within the B cell follicle and the GC.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"64"},"PeriodicalIF":33.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247829","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}

{"title":"Genetic tracing uncovers the importance of epithelial-to-mesenchymal transition in small cell lung cancer chemotherapy resistance but not metastasis.","authors":"Yuting Chen, Chenchen Guo, Xinlei Cai, Liang Hu, Xinyuan Tong, Yun Xue, Qiqi Zhao, Tengfei Zhang, Yuan Chen, Yongting Fang, Yayi He, Yan Li, Bin Zhou, Hongbin Ji","doi":"10.1038/s41421-024-00687-8","DOIUrl":"10.1038/s41421-024-00687-8","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"60"},"PeriodicalIF":33.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247744","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}

{"title":"Publisher Correction: SGF29 nuclear condensates reinforce cellular aging.","authors":"Kaowen Yan, Qianzhao Ji, Dongxin Zhao, Mingheng Li, Xiaoyan Sun, Zehua Wang, Xiaoqian Liu, Zunpeng Liu, Hongyu Li, Yingjie Ding, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu","doi":"10.1038/s41421-024-00690-z","DOIUrl":"10.1038/s41421-024-00690-z","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"61"},"PeriodicalIF":33.5,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178995","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}

{"title":"IFRD1 promotes tumor cells \"low-cost\" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.","authors":"Yabin Huang, Fanzheng Meng, Taofei Zeng, Rick Francis Thorne, Lifang He, Qingrui Zha, Hairui Li, Hong Liu, Chuandong Lang, Wanxiang Xiong, Shixiang Pan, Dalong Yin, Mian Wu, Xuedan Sun, Lianxin Liu","doi":"10.1038/s41421-024-00668-x","DOIUrl":"10.1038/s41421-024-00668-x","url":null,"abstract":"<p><p>Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"57"},"PeriodicalIF":33.5,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157935","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}