{"title":"Correction to: Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells.","authors":"","doi":"10.1093/jmcb/mjaf012","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf012","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phase separation of hnRNPA1 and TERRA regulates telomeric stability.","authors":"Ziyan Xu, Yongrui Liu, Fudong Li, Yi Yang, Hong Zhang, Feilong Meng, Xing Liu, Xin Xie, Xianjun Chen, Yunyu Shi, Liang Zhang","doi":"10.1093/jmcb/mjae037","DOIUrl":"10.1093/jmcb/mjae037","url":null,"abstract":"<p><p>Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. hnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for >20 years. Here, our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1, while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307933","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}
Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real
{"title":"HIV-1 inhibits IFITM3 expression to promote the infection of megakaryocytes.","authors":"Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real","doi":"10.1093/jmcb/mjae042","DOIUrl":"10.1093/jmcb/mjae042","url":null,"abstract":"<p><p>Despite an undetectable plasma viral load as a result of antiretroviral therapy, HIV-1-infected individuals with poor immune reconstitution harbor infectious HIV-1 within their platelets. Megakaryocytes, as platelet precursors, are the likely cellular origin of these HIV-1-containing platelets. To investigate the mechanisms that allow megakaryocytes to support HIV-1 infection, we established in vitro models of viral infection using hematopoietic stem cell-derived megakaryocytes and the megakaryocytic MEG-01 cell line. We observed HIV-1 DNA provirus integration into the megakaryocyte cell genome, self-limiting virus production, and HIV-1 protein and RNA compartmentalization, which are hallmarks of HIV-1 infection in myeloid cells. In addition, following HIV-1 infection of megakaryocyte precursors, the expression of interferon-induced transmembrane protein 3 (IFITM3), an antiviral factor constitutively expressed in megakaryocytes, was inhibited in terminally differentiated HIV-1-infected megakaryocytes. IFITM3 knockdown in MEG-01 cells prior to infection led to enhanced HIV-1 infection, indicating that IFITM3 acts as an HIV-1 restriction factor in megakaryocytes. Together, these findings indicate that megakaryocyte precursors are susceptible to HIV-1 infection, leading to terminally differentiated megakaryocytes harboring virus in a process regulated by IFITM3. Megakaryocytes may thus constitute a neglected HIV-1 reservoir that warrants further study in order to develop improved antiretroviral therapies and to facilitate HIV-1 eradication.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361586","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}
Jianyu Yang, Fulin Xing, Fen Hu, Mengdi Hou, Hao Dong, Jiayu Cheng, Wan Li, Rui Yan, Jingjun Xu, Ke Xu, Leiting Pan
{"title":"Super-resolution microscopy unveils the nanoscale organization and self-limiting clustering of CD47 in human erythrocytes.","authors":"Jianyu Yang, Fulin Xing, Fen Hu, Mengdi Hou, Hao Dong, Jiayu Cheng, Wan Li, Rui Yan, Jingjun Xu, Ke Xu, Leiting Pan","doi":"10.1093/jmcb/mjae041","DOIUrl":"10.1093/jmcb/mjae041","url":null,"abstract":"<p><p>The transmembrane protein CD47, an innate immune checkpoint protein, plays a pivotal role in preventing healthy erythrocytes from immune clearance. Our study utilized stochastic optical reconstruction microscopy (STORM) and single-molecule analysis to investigate the distribution of CD47 on the human erythrocyte membrane. Contrary to previous findings in mouse erythrocytes, we discovered that CD47 exists in randomly distributed monomers rather than in clusters across the human erythrocyte membrane. Using secondary antibody-induced crosslinking, we found that CD47 aggregates into stable clusters within minutes. By comparing these STORM results with those of the fully mobile protein CD59 and the cytoskeleton-bound membrane protein glycophorin C under similar conditions, as well as devising two-color STORM co-labeling and co-clustering experiments, we further quantitatively revealed an intermediate, self-limiting clustering behavior of CD47, elucidating its fractional (∼14%) attachment to the cytoskeleton. Moreover, we report reductions in both the amount of CD47 and its clustering capability in aged erythrocytes, providing new insight into erythrocyte senescence. Together, the combination of STORM and secondary antibody-based crosslinking unveils the unique self-limiting clustering behavior of CD47 due to its fractional cytoskeleton attachment.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375579","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}
Wang Luo, Fang Zhang, Fangzhen Zhao, Yang Fang, Long Zhao, Ying Su
{"title":"Dual role of PpV in Drosophila crystal cell proliferation and survival.","authors":"Wang Luo, Fang Zhang, Fangzhen Zhao, Yang Fang, Long Zhao, Ying Su","doi":"10.1093/jmcb/mjae028","DOIUrl":"10.1093/jmcb/mjae028","url":null,"abstract":"<p><p>Drosophila melanogaster crystal cells are a specialized type of blood cells for the innate immune process upon injury. Under normal conditions, crystal cells rarely proliferate and constitute a small proportion of fly blood cells. Notch signaling has been known to guide the cell fate determination of crystal cells and maintain their survival. Here, we reported that protein phosphatase V (PpV), the unique catalytic subunit of protein phosphatase 6 in Drosophila, is a novel regulator of crystal cell proliferation and integrity. We found that PpV proteins highly accumulated in crystal cells in the larval hematopoietic organ termed the lymph gland. Silencing PpV using RNA interference led to increased crystal cell proliferation in a Notch-independent manner and induced crystal cell rupture dependent on Notch signaling. Moreover, additive PpV prevented the rupture of crystal cells in lymph glands upon a needle injury, suggesting the involvement of PpV in wound healing. Altogether, our results indicated that PpV plays a dual role in lymph glands, preventing crystal cell proliferation to limit the cell number, as well as inhibiting crystal cell rupture to maintain their survival.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860068","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}
Wenya Yu, Xiang Liu, Hong Chen, Jiahe Tian, Meina Li, Wei Mu, Yang Ge
{"title":"Gender differences in the health workforce in China: an analysis of national data.","authors":"Wenya Yu, Xiang Liu, Hong Chen, Jiahe Tian, Meina Li, Wei Mu, Yang Ge","doi":"10.1093/jmcb/mjae040","DOIUrl":"10.1093/jmcb/mjae040","url":null,"abstract":"<p><p>Gender differences in the health workforce matter for women's health and healthcare, and is also crucial for both health and economic development. Drawing on limited national gender data from China over the last 10 years, during which the country was undergoing a healthcare reform, this study dissects gender-related issues to identify existing problems, monitor progress, and develop strategies to promote change. Although women constituted the majority of health workers, they are predominantly engaged in service-oriented occupations. The gender distribution substantially differed between urban and rural primary health institutions. Moreover, significant differences in gender distribution among professional public health institutions were observed. The gender distribution of administrators varied in different types of health institutions. Women had lighter workloads because of the imbalanced distribution of specialties. Academicians comprised very few female scientists. To promote a more balanced gender distribution, policies should be developed to encourage a more reasonable division of family responsibilities. Further, equal higher education opportunities should be ensured for girls, especially in rural areas. Solutions to free more women from work-marriage-childcare conflicts and to decrease turnover rates deserve further discussion. Gender data should be highlighted and optimized to further advance gender differences among the health workforce and for women's health in China.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391201","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":"Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage.","authors":"Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li","doi":"10.1093/jmcb/mjaf002","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf002","url":null,"abstract":"<p><p>The Wnt signaling pathway plays important roles in cardiomyocyte proliferation and cardiac regeneration after heart injury. Abnormal activation of the Wnt pathway causes a reduction of cardiomyocyte function, leading to hypertrophy, fibrosis, and heart failure. However, the mechanism through which Wnt signaling affects cardiomyocyte function during cardiac diseases is still unclear. In this study, we observed that activation of the Wnt/β-catenin pathway, but not the Wnt/Ca2+ pathway, leads to significant cytosol calcium enrichment. Such an effect can be inhibited by cycloheximide that blocks the downstream gene expression. By analyzing the transcriptome data, we found that activation of the Wnt/β-catenin pathway significantly upregulates the expression level of muscle-selective A kinase anchoring protein (mAKAP, also called AKAP6), a scaffold protein that can improve the interaction between PKA and its substrate ryanodine receptor 2 (RyR2) in cardiomyocytes. We further identified that AKAP6 is a target gene of the canonical Wnt pathway and increasing AKAP6 expression can enhance RyR2 phosphorylation by PKA, causing the sarcoplasmic reticulum calcium leakage and finally heart dysfunction. Our finding that the Wnt/β-catenin pathway affects cardiac calcium regulation via AKAP6 and RyR2 provides profound insights into heart diseases and sheds light on potential therapeutic strategies.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daoxu Wu, Shijiu Lu, Jiaying Hu, Ming Zeng, Jingjing Wu, Cui Li, Xingfang Tang, Tian Lu, Yi Zhu, Jiayin Liu, Lianju Qin, Ningning Wang
{"title":"Calciphylaxis: Ongoing Challenges and Treatment Opportunities with Mesenchymal Stem Cells.","authors":"Daoxu Wu, Shijiu Lu, Jiaying Hu, Ming Zeng, Jingjing Wu, Cui Li, Xingfang Tang, Tian Lu, Yi Zhu, Jiayin Liu, Lianju Qin, Ningning Wang","doi":"10.1093/jmcb/mjaf009","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf009","url":null,"abstract":"<p><p>Calciphylaxis is a rare, progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications, microthrombi, and endothelial damage. It mainly affects patients with chronic kidney disease (CKD), which is also known as calcific uremic arteriolopathy. Skin biopsy is the gold standard for diagnosis, but it is an invasive procedure. Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate. A multidisciplinary targeted approach is the primary treatment method. Vascular calcification, which is a common complication in patients with CKD, cannot completely explain the rapid progression of calciphylaxis. This article reviews the advances in the epidemiological characteristics, risk factors, and diagnosis, including non-uraemic calciphylaxis (NUC) and visceral calciphylaxis, pathogenesis, associated animal models, and treatment of calciphylaxis. The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis. The acute effects on progressive vascular injury, including the induction of severe ischemia and inflammatory responses, have been emphasized. Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies. Mesenchymal stem cells (MSCs) may be proposed as a novel therapy for calciphylaxis because of their regenerative effects, inhibition of vascular calcification, anti-infection and immunomodulation properties, and improvement of hypercoagulability. Safe, effective, accessible, and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianyang Luo, Zhiyuan Shi, Haibin Yang, Jiafan Miao, Zilong Chang, Jie Zou, Qiang Zeng, Wenbin Wu, Yanan Jiang, Xiaoling Xie, Liu Cao, Hong Peng, Chunmei Li, Deyin Guo, Junyu Wu
{"title":"Characterization of the nucleolar localization signal of TRMT10A and its importance for the m1G9 methylation of tRNAs in mammalian cells.","authors":"Tianyang Luo, Zhiyuan Shi, Haibin Yang, Jiafan Miao, Zilong Chang, Jie Zou, Qiang Zeng, Wenbin Wu, Yanan Jiang, Xiaoling Xie, Liu Cao, Hong Peng, Chunmei Li, Deyin Guo, Junyu Wu","doi":"10.1093/jmcb/mjaf011","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf011","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}