Journal of Molecular Cell Biology最新文献

Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage. Wnt/β-catenin通路通过akap6介导的RyR2磷酸化和肌浆网钙渗漏诱导心功能障碍。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf002

Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li

{"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":"10.1093/jmcb/mjaf002","url":null,"abstract":"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 in 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 protein kinase A (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.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301655/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comments on 'Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages'. “巨噬细胞对细胞外基质的降解是由维门蛋白中间丝协调肌动蛋白应激纤维和足小体决定的”。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf004

Sandrine Etienne-Manneville

引用次数: 0

METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell. METTL3通过维持Lgr5+干细胞的自我更新和分化来调节结肠上皮的完整性。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjae060

Chenbo Ding, Xinhui Yang, Hua Liu, Manolis Roulis, Huifang Chen, Yunzhu Chen, Hao Xu, Yimeng Gao, Jie Zhong, Hua-Bing Li, Youqiong Ye, Wei Cai, Weiguo Hu, Zhengting Wang

{"title":"METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell.","authors":"Chenbo Ding, Xinhui Yang, Hua Liu, Manolis Roulis, Huifang Chen, Yunzhu Chen, Hao Xu, Yimeng Gao, Jie Zhong, Hua-Bing Li, Youqiong Ye, Wei Cai, Weiguo Hu, Zhengting Wang","doi":"10.1093/jmcb/mjae060","DOIUrl":"https://doi.org/10.1093/jmcb/mjae060","url":null,"abstract":"The development and homeostasis of intestinal epithelium are mediated by actively proliferating Lgr5+ stem cells, which possess a remarkable self-renewal and differentiation capacity. Recently, our study demonstrated that N6-methyladenosine (m6A) methylation was essential for the survival of colonic stem cells. Here, we show that methyltransferase-like 3 (METTL3) expression is downregulated in the colon mucosa in ulcerative colitis (UC) patients and strongly associated with the differentiation and maturation of goblet cells during inflammation. In mice, depletion of Mettl3 significantly inhibits the self-renewal and differentiation of Lgr5+ stem cells, especially the differentiation and maturation of goblet cells, resulting in intestinal dysplasia and spontaneous inflammation. Mechanistically, Mettl3 deletion-mediated m6A loss facilitates the expression levels of growth factor receptor binding protein 10 (Grb10) and interferon-related developmental regulator 1 (Ifrd1) via increasing their messenger RNA stability. We further demonstrate that the levels of GRB10 and IFRD1 are negatively correlated with METTL3 level in UC samples. Collectively, our data indicate that METTL3 enhances the self-renewal and differentiation of Lgr5+ stem cells during intestinal development and inflammation, and thus it may be a potential therapeutic target for UC treatment.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":"17 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742331","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}

引用次数: 0

Phosphorylation of CENP-C by PLK1 ensures accurate chromosome congression during mitosis. PLK1对CENP-C的磷酸化确保了有丝分裂期间染色体的准确聚集。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjae062

Shanshan He, Cunyu Wang, Hengyi Shao, Chengcheng Hu, Ranran Hu, Ran Liu, Changlu Tao, Chao Wang, Chuanhai Fu, Xing Liu, Xuebiao Yao, Liangyu Zhang

引用次数: 0

The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement. 机械反应性染色体乘客复合体在限制下维持沟侵入。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-22 DOI: 10.1093/jmcb/mjaf019

Chenxin Wang, Jingjing Ding, Chao Wang, Maiyong Zhang, Junjie Wu, Bowen Chen, Hui Yang, Ting Gang Chew

{"title":"The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement.","authors":"Chenxin Wang, Jingjing Ding, Chao Wang, Maiyong Zhang, Junjie Wu, Bowen Chen, Hui Yang, Ting Gang Chew","doi":"10.1093/jmcb/mjaf019","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf019","url":null,"abstract":"Cells sense and respond to forces from neighbouring cells and the extracellular matrix during growth and division. When cells undergo mitosis in a confined environment like in tumour environment, high compressive stress causes unstable cell cortex and prolonged mitosis. Confined mitotic cells frequently experience chromosome loss and multipolar division. How the cortical instability affects cytokinesis under confinement is unclear. Here, we show that confined mitotic cells undergo furrow ingression comparable to unconfined mitotic cells but are strongly reliant on Aurora B kinase, a catalytic subunit of the chromosomal passenger complex (CPC) for its completion. Mechanistically, the cortical pool of CPC via the scaffolding protein INCENP sustains Aurora B at the equatorial cortex to drive furrow ingression under confinement. We identified mechanoresponsive elements within the single alpha-helix (SAH) domain of INCENP that maintain the cortical CPC at the equatorial cortex to promote furrow ingression in response to high compressive stress. Thus, the cortical INCENP not only binds to actin filaments but also mechanically respond to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690560","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}

引用次数: 0

cGAS: Bridging Immunity and Metabolic Regulation. 桥接免疫和代谢调节。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-17 DOI: 10.1093/jmcb/mjaf018

Jing Wang, Wen Meng

引用次数: 0

The disruption of COPII vesicles activates HSF-1 through SEC-23. COPII囊泡的破坏通过SEC-23激活HSF-1。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-03 DOI: 10.1093/jmcb/mjaf017

Zhidong He, Na Tang, Hao Liu, Xueqing Wang, Yue Yin, Chao Peng, Yidong Shen

引用次数: 0

ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism. eno1 - bace2介导的LDLR裂解通过重塑胆固醇代谢促进肝癌进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-06-28 DOI: 10.1093/jmcb/mjaf001

Zhikun Li, Kaixiang Fan, Caixia Suo, Xuemei Gu, Chuxu Zhu, Haoran Wei, Liang Chen, Ping Gao, Linchong Sun

{"title":"ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.","authors":"Zhikun Li, Kaixiang Fan, Caixia Suo, Xuemei Gu, Chuxu Zhu, Haoran Wei, Liang Chen, Ping Gao, Linchong Sun","doi":"10.1093/jmcb/mjaf001","DOIUrl":"10.1093/jmcb/mjaf001","url":null,"abstract":"Enolase 1 (ENO1) is a glycolytic enzyme involved in tumour progression that performs a variety of classical and nonclassical functions. However, the mechanism by which it promotes tumour progression is still not fully understood. Here, we found that ENO1 can bind to β-site amyloid precursor protein cleaving enzyme 2 (BACE2), a codependent gene of ENO1, in liver cancer cells. By suppressing lysosomal-dependent degradation, ENO1 stabilizes BACE2 protein level without affecting its messenger RNA level. Further analysis revealed that ENO1 and BACE2 promote low-density lipoprotein receptor (LDLR) cleavage, leading to decreased absorption of exogenous cholesterol. To maintain intracellular cholesterol levels, ENO1 and BACE2 upregulate the expression of genes involved in de novo cholesterol synthesis through a negative feedback mechanism. Both in vitro and in vivo, BACE2 mediates the tumour-promoting effect of ENO1 in liver cancer. Finally, high expression levels of ENO1 and BACE2 and low expression levels of LDLR were detected in clinical hepatocellular carcinoma samples, and abnormal expression of the ENO1-BACE2-LDLR axis was significantly associated with poor prognosis in patients with liver cancer. These data collectively demonstrated that ENO1 functions in protein cleavage by binding to BACE2 and promotes liver cancer progression by reprogramming cholesterol metabolism.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365117","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}

引用次数: 0

Novel roles of ammonia in physiology and cancer. 氨在生理和癌症中的新作用。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-06-28 DOI: 10.1093/jmcb/mjaf007

Guantong Chen, Chenxi Wang, Shuo Huang, Shibo Yang, Qiyuan Su, Yige Wang, Weiwei Dai

{"title":"Novel roles of ammonia in physiology and cancer.","authors":"Guantong Chen, Chenxi Wang, Shuo Huang, Shibo Yang, Qiyuan Su, Yige Wang, Weiwei Dai","doi":"10.1093/jmcb/mjaf007","DOIUrl":"10.1093/jmcb/mjaf007","url":null,"abstract":"Ammonia, traditionally recognized as a toxic nitrogen waste product, has recently emerged as a significant player in diverse physiological processes and implicated in cancer biology. This review article provides an overview of the multifaceted impact of ammonia on cellular signaling pathways, energy metabolism, and tumor microenvironment dynamics, in particular its novel roles in neurotransmission, metabolic homeostasis, cancer cell proliferation, and immune modulation. Notably, ammonia accumulates within the tumor microenvironment, promoting nonessential amino acid synthesis, stimulating mTORC1 activation, promoting lipid synthesis, and impairing various immune cell functions, thereby promoting tumor progression. Furthermore, the potential dual role of ammonia as a tumorigenic factor and a cancer therapeutic target is discussed, shedding light on its complex regulatory mechanisms and clinical implications. This timely review aims to deepen our understanding of the emerging physiological and pathological roles of ammonia, offering valuable insights into its significance as a potential target for diagnostic and therapeutic interventions in cancer and beyond.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573275","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}

引用次数: 0

Inhibition of EphA2 by syndecan-4 in wounded skin regulates clustering of fibroblasts. syndecan-4在损伤皮肤中抑制EphA2可调节成纤维细胞的聚集。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-06-28 DOI: 10.1093/jmcb/mjae054

Rebecca Brooks, Xianhui Wei, Mang Leng Lei, Francisca Cisterna Cid, James A Roper, Rosalind C Williamson, Mark D Bass

{"title":"Inhibition of EphA2 by syndecan-4 in wounded skin regulates clustering of fibroblasts.","authors":"Rebecca Brooks, Xianhui Wei, Mang Leng Lei, Francisca Cisterna Cid, James A Roper, Rosalind C Williamson, Mark D Bass","doi":"10.1093/jmcb/mjae054","DOIUrl":"10.1093/jmcb/mjae054","url":null,"abstract":"Upon injury, fibroblasts in the surrounding tissue become activated, migrating into the wound in a controlled manner. Once they arrive, they contract the wound and remodel the stroma. While certain cell surface receptors promote fibroblast migration, others cause repulsion between fibroblasts upon contact, seemingly opposing their clustering within the wound bed. Eph receptor-ephrin interactions on colliding cells trigger this repulsion, but how fibroblasts transition to clustering behaviour during healing remains unclear. Syndecan-4 modulates transmembrane receptors involved in wound healing, including receptors for the extracellular matrix and growth factors. As a result, Sdc4-/- mice experience delayed healing due to impaired fibroblast recruitment. In this study, we report that syndecan-4 also regulates fibroblast repulsion during wound healing. We discover that syndecan-4 inhibits the expression and signalling of EphA2 by activating PKCα. Changes in syndecan-4 expression, such as those observed during wound healing, alter fibroblast behaviour from repulsion to adhesion upon cell collision by modulating EphA2 levels. Moreover, we find that EphA2 expression is suppressed in wound bed fibroblasts in a syndecan-4-dependent manner, explaining how fibroblast clustering is achieved during wound healing.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882413","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}

引用次数: 0