Journal of cell science最新文献_第2页

A Cryo-Electron Microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface. 酵母Pex5与货物复合物的低温电镜结构揭示了一个新的结合界面。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-16 DOI: 10.1242/jcs.263890

Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar

{"title":"A Cryo-Electron Microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface.","authors":"Lior Peer, Orly Dym, Nadav Elad, Asa Tirosh, Jossef Jacobovitch, Ehud Sivan, Mor Angel, Shira Albeck, Maya Schuldiner, Yoav Peleg, Einat Zalckvar","doi":"10.1242/jcs.263890","DOIUrl":"https://doi.org/10.1242/jcs.263890","url":null,"abstract":"Proper protein targeting to organelles is crucial for maintaining eukaryotic cellular function and homeostasis. This necessity has driven the evolution of specific targeting signals on proteins and the targeting factors that recognize them. A prominent example is peroxisomal matrix proteins, most of which depend on the targeting factor Pex5 to localize and function correctly. While most Pex5 cargoes contain a Peroxisomal Targeting Signal type 1 (PTS1), they are not all targeted similarly. Some undergo priority targeting, facilitated either by stronger binding to specific subsets of PTS1 signals or by additional interaction interfaces. These observations highlight the extensive complexity of Pex5-mediated targeting. In this study, we reveal that the matrix protein Eci1 can reach peroxisomes and bind Pex5 in the absence of PTS1. By solving the structure of the yeast Pex5-Eci1 complex using Cryo-Electron Microscopy, we identified additional binding interfaces. Our findings provide new insights into the versatile interactions between Pex5 and its cargo, Eci1. More broadly, this work highlights the intricate, dynamic nature of the interactions between cargo factors and their cargoes to meet the complex environment within eukaryotic cells.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A data-driven model for mitochondrial inner membrane remodeling as a driving force of organelle shaping. 线粒体内膜重塑作为细胞器形成驱动力的数据驱动模型。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 DOI: 10.1242/jcs.263850

Noga Preminger, Ben Zucker, Sarah Hassdenteufel, Till Stephan, Stefan Jakobs, Michael M Kozlov, Maya Schuldiner

{"title":"A data-driven model for mitochondrial inner membrane remodeling as a driving force of organelle shaping.","authors":"Noga Preminger, Ben Zucker, Sarah Hassdenteufel, Till Stephan, Stefan Jakobs, Michael M Kozlov, Maya Schuldiner","doi":"10.1242/jcs.263850","DOIUrl":"https://doi.org/10.1242/jcs.263850","url":null,"abstract":"Mitochondria are dynamic organelles exhibiting diverse shapes. While the variation of shapes, ranging from spheres to elongated tubules, and the transition between them, are clearly seen in many cell types, the molecular mechanisms governing this morphological variability remain poorly understood. Here, we propose a biophysical model for the shape transition between spheres and tubules based on the interplay between the inner and outer mitochondrial membranes. Our model suggests that the difference in surface area, arising from the folding of the inner membrane into cristae, correlates with mitochondrial elongation. Analysis of live cell super-resolution microscopy data supports this correlation, linking elongated shapes to the extent of cristae in the inner membrane. Knocking down cristae shaping proteins further confirms the impact on mitochondrial shape, demonstrating that defects in cristae formation correlate with mitochondrial sphericity. Our results suggest that the dynamics of the inner mitochondrial membrane are important not only for simply creating surface area required for respiratory capacity, but go beyond that to affect the whole organelle morphology. This work explores the biophysical foundations of individual mitochondrial shape, suggesting potential links between mitochondrial structure and function. This should be of profound significance, particularly in the context of disrupted cristae shaping proteins and their implications in mitochondrial diseases.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Correction: Defining the dynamin-based ring organizing center on the peroxisome-dividing machinery isolated from Cyanidioschyzon merolae. 修正：定义从矢车菊中分离的过氧化物酶体分裂机制上的动力蛋白环组织中心。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-19 DOI: 10.1242/jcs.264019

Yuuta Imoto, Yuichi Abe, Kanji Okumoto, Masanori Honsho, Haruko Kuroiwa, Tsuneyoshi Kuroiwa, Yukio Fujiki

引用次数: 0

Cell deformations generated by stochastic actomyosin waves drive in vivo random-walk swimming migration. 随机肌动蛋白波产生的细胞变形驱动体内随机游动迁移。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-22 DOI: 10.1242/jcs.263787

Cyril Andrieu, Bren Hunyi Lee, Anna Franz

{"title":"Cell deformations generated by stochastic actomyosin waves drive in vivo random-walk swimming migration.","authors":"Cyril Andrieu, Bren Hunyi Lee, Anna Franz","doi":"10.1242/jcs.263787","DOIUrl":"10.1242/jcs.263787","url":null,"abstract":"Amoeboid cell migration drives many developmental and disease-related processes, including immune responses and cancer metastasis. Swimming migration is a subtype of amoeboid migration that is observed in cells in suspension ex vivo. However, the mechanism underlying swimming migration in vivo is unknown. Using Drosophila fat body cells (FBCs) as a model, we show that FBCs actively swim to patrol the pupa by random walk. Their migration is powered through actomyosin waves that exert compressive forces as they travel to the cell rear, causing cell deformations. Unlike in other types of amoeboid migration, Rho1 (the Drosophila orthologue of RhoA), Cdc42 and Rac1 are all required for regulation of formin-driven actin polymerization during FBC migration. We find that Rho1 at the cell rear induces actomyosin contractions via Rho kinase and myosin II. We show that contractile actin waves display a stochastic behaviour, inducing either cell elongation or rounding, suggesting that non-reciprocal cell deformations drive locomotion. Importantly, our work in a physiological system reveals that stochastic actomyosin waves promote random-walk swimming migration to enable fast, long-range cell dispersal. We propose that this individualist migration behaviour collectively allows patrolling of the pupal body.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The STEAP4 target NQO1 mediates colon tumorigenesis. STEAP4靶点NQO1介导结肠肿瘤发生。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-22 DOI: 10.1242/jcs.263402

Kunlun Yin, Luke Villareal, Xiangxiang Wu, Mariella Arcos, Jordan Lee, David R Martin, Julie G In, Kimberly Leslie, Donna D Zhang, Xiang Xue

{"title":"The STEAP4 target NQO1 mediates colon tumorigenesis.","authors":"Kunlun Yin, Luke Villareal, Xiangxiang Wu, Mariella Arcos, Jordan Lee, David R Martin, Julie G In, Kimberly Leslie, Donna D Zhang, Xiang Xue","doi":"10.1242/jcs.263402","DOIUrl":"10.1242/jcs.263402","url":null,"abstract":"Colorectal cancer (CRC) remains a major global health concern, necessitating advancements in therapeutic strategies. Understanding the mechanisms driving CRC is crucial for developing effective treatments. Previous studies, including our own, highlight the role of six-transmembrane epithelial antigen of prostate 4 (STEAP4) in promoting colon tumorigenesis through reactive oxygen species (ROS) generation, making it a promising target. Our research provides compelling evidence that STEAP4 knockout significantly reduces colon tumorigenesis in a genetically engineered mouse model. Suppressing STEAP4 via knockdown techniques effectively attenuated the nuclear factor erythroid 2-related factor 2 (NRF2)-NAD(P)H:quinone oxidoreductase 1 (NQO1) signaling pathway, inducing apoptosis and autophagy, leading to substantial reductions in xenograft tumor growth. In contrast, STEAP4 overexpression amplified ROS production and activated the NRF2-NQO1 pathway in a ferric iron (Fe3+)-dependent manner. Notably, bioactivatable drugs targeting NQO1 were highly effective at eradicating STEAP4-overexpressing colon cancer cells. These findings highlight the potential of targeted therapeutic interventions for CRC, particularly through STEAP4 modulation. In conclusion, our study advances understanding of the role of STEAP4 in colon tumorigenesis, offering promising avenues for novel CRC treatments.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Quantitative comparison of fluorescent proteins using protein nanocages in live cells. 利用蛋白纳米笼在活细胞中定量比较荧光蛋白。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-21 DOI: 10.1242/jcs.263858

Giulia Viola, Yasmeen W Ibrahim, Kyle A Jacobs, Joël Lemière, Matthew L Kutys, Torsten Wittmann

{"title":"Quantitative comparison of fluorescent proteins using protein nanocages in live cells.","authors":"Giulia Viola, Yasmeen W Ibrahim, Kyle A Jacobs, Joël Lemière, Matthew L Kutys, Torsten Wittmann","doi":"10.1242/jcs.263858","DOIUrl":"10.1242/jcs.263858","url":null,"abstract":"To standardize comparison of fluorescent protein performance on a molecule-by-molecule basis in a physiological intracellular environment, we constructed fluorescent protein-tagged I3-01 peptides that self-assemble into stable 60-subunit dodecahedrons inside live mammalian cells. We were especially interested in determining which of the recently published monomeric StayGold variants is best for live microscopy in mammalian cells. Combining nanocage brightness and photobleaching measurements into a single metric, mStayGold stood out as far superior to all other green and red fluorescent proteins we tested with a functional lifetime that is at least 8-10-fold longer compared with EGFP or mEmerald. Analysis of intracellular nanocage diffusion further confirmed the monomeric nature of mStayGold, and we demonstrate that mStayGold-tagged nanocages can serve as highly photostable nanoparticles to analyze intracellular biophysical properties. Analysis of frequently used red fluorescent proteins was less encouraging and recent mScarlet or mRuby variants did not perform substantially better than mCherry on a typical spinning disc confocal microscope system, highlighting the importance of a standardized method to benchmark fluorescent proteins to make optimal choices for specific experimental setups.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Tumor acidosis supports cancer cell lipid uptake via a rapid transporter-independent mechanism. 肿瘤酸中毒通过一种快速的、不依赖于转运蛋白的机制支持癌细胞脂质摄取。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 DOI: 10.1242/jcs.263688

Marc Severin, Rikke K Hansen, Michala G Rolver, Tove Hels, Kenji Maeda, Luis A Pardo, Stine F Pedersen

{"title":"Tumor acidosis supports cancer cell lipid uptake via a rapid transporter-independent mechanism.","authors":"Marc Severin, Rikke K Hansen, Michala G Rolver, Tove Hels, Kenji Maeda, Luis A Pardo, Stine F Pedersen","doi":"10.1242/jcs.263688","DOIUrl":"10.1242/jcs.263688","url":null,"abstract":"Tumor acidosis alters cancer cell metabolism and favors aggressive disease progression. Cancer cells in acidic environments increase lipid droplet accumulation and oxidative phosphorylation, which are characteristics of aggressive cancers. Here, we used live imaging, shotgun lipidomics and immunofluorescence analyses of mammary and pancreatic cancer cells to demonstrate that both acute acidosis and adaptation to acidic growth drive rapid uptake of fatty acids (FAs), which are converted to triacylglycerols and stored in lipid droplets. Consistent with being independent of de novo synthesis, triacylglycerol and lipid droplet accumulation in acid-adapted cells was unaffected by FA synthetase (FAS, encoded by FASN) inhibitors. Macropinocytosis, which is upregulated in acid-adapted cells, partially contributed to FA uptake, which was independent of other protein-facilitated lipid uptake mechanisms, including uptake via CD36 and FATP2, and caveolin- and clathrin-dependent endocytosis. We propose that a major mechanism by which tumor acidosis drives FA uptake is through neutralizing protonation of negatively charged FAs allowing their diffusive, transporter-independent uptake. We suggest that this could be a major factor triggering acidosis-driven metabolic rewiring.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Enhancement of CEP215 dynamics for spindle pole assembly during mitosis. 有丝分裂过程中CEP215/CDK5RAP2对纺锤杆组装的动力学增强。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-21 DOI: 10.1242/jcs.263542

Hyunjeong Yoo, Taehyun Kim, Sungjin Ryu, Donghee Ko, Jeesoo Kim, Hee-Jung Choi, Yongdae Shin, Kunsoo Rhee

{"title":"Enhancement of CEP215 dynamics for spindle pole assembly during mitosis.","authors":"Hyunjeong Yoo, Taehyun Kim, Sungjin Ryu, Donghee Ko, Jeesoo Kim, Hee-Jung Choi, Yongdae Shin, Kunsoo Rhee","doi":"10.1242/jcs.263542","DOIUrl":"10.1242/jcs.263542","url":null,"abstract":"The microtubule-organizing activity of centrosomes fluctuates during the cell cycle, reaching the highest levels at M phase. CEP215 (also known as CDK5RAP2) is a key pericentriolar material (PCM) protein for microtubule organization of the human centrosome. Here, we provide evidence that CEP215 exhibits a dynamically suppressed, solid-like state in interphase centrosomes, and becomes a more dynamic state in mitotic centrosomes. Specific interaction with PCNT, another centrosome protein, is crucial for diffusible molecular dynamicity of the CEP215 protein. We also found that the cluster formation activity of CEP215 is impaired in a light-inducible system when its coiled-coil domains (CCDs) are truncated. Defects in spindle pole assembly and spindle formation were accompanied in the cells whose CEP215 is replaced with the CCD-truncated mutants. Our results support the notion that the diffusible mobility of CEP215 is enhanced by both homotypic and heterotypic interactions among CCDs, especially at mitotic spindle poles. This work highlights that biophysical properties of the PCM proteins at the centrosomes fluctuate during the cell cycle.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The phosphorylation of Pak1 by Erk1/2 to drive cell migration requires Arl4D acting as a scaffolding protein. Erk1/2磷酸化Pak1以促进细胞迁移需要Arl4D作为支架蛋白。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-22 DOI: 10.1242/jcs.263812

Ting-Wei Chang, Ming-Chieh Lin, Chia-Jung Yu, Fang-Jen S Lee

{"title":"The phosphorylation of Pak1 by Erk1/2 to drive cell migration requires Arl4D acting as a scaffolding protein.","authors":"Ting-Wei Chang, Ming-Chieh Lin, Chia-Jung Yu, Fang-Jen S Lee","doi":"10.1242/jcs.263812","DOIUrl":"10.1242/jcs.263812","url":null,"abstract":"Activation of extracellular signal-regulated kinases 1 and 2 (Erk1/2; also known as MAPK3 and MAPK1, respectively) at the plasma membrane usually leads to their translocation to various intracellular sites, where scaffolding proteins mediate substrate targeting. However, in platelet-derived growth factor (PDGF)-induced signaling, Erk1/2 phosphorylate Pak1 to drive cell migration while remaining at the plasma membrane, raising the question of whether scaffolding proteins are required. Similarly, the small GTPase Arf-like protein 4D (Arl4D) promotes cell migration by recruiting Pak1 to the plasma membrane and facilitating its phosphorylation, although the mechanism linking recruitment to phosphorylation remains unclear. To address these questions, we show that Arl4D functions as a scaffolding protein by recruiting Erk1/2 and Pak1 to the plasma membrane, assembling them into a functional complex. This complex allows Erk1/2 to phosphorylate Pak1, supporting the role of the latter in cell migration. Our findings identify Arl4D as a novel regulator of Erk1/2, reveal a conserved role of scaffolding proteins in Erk1/2 substrate targeting, and uncover an unrecognized interplay among Arl4D, Erk1/2 and Pak1. These insights provide a deeper understanding of the molecular coordination underlying Pak1-mediated cell migration and its regulation by Erk1/2 and Arl4D.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

PI31 is a positive regulator of 20S immunoproteasome assembly. PI31是20S免疫蛋白酶体组装的正调节因子。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-23 DOI: 10.1242/jcs.263887

Jason Wang, Abbey Kjellgren, George N DeMartino

引用次数: 0