Journal of cell science最新文献_第10页

14-3-3ε inhibits premature centriole disengagement by inhibiting the activity of Plk1 and separase. 14-3-3通过抑制Plk1和分离酶活性抑制中心粒过早脱离。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-07-15 Epub Date: 2025-07-18 DOI: 10.1242/jcs.263808

Monika A Jaiswal, Akshay Karn, Aparna Das, Anisha Kumari, Shilu Tiwari, Sorab N Dalal

{"title":"14-3-3ε inhibits premature centriole disengagement by inhibiting the activity of Plk1 and separase.","authors":"Monika A Jaiswal, Akshay Karn, Aparna Das, Anisha Kumari, Shilu Tiwari, Sorab N Dalal","doi":"10.1242/jcs.263808","DOIUrl":"10.1242/jcs.263808","url":null,"abstract":"The 14-3-3 protein family regulates several pathways in mammalian cells, including centrosome duplication. However, the precise mechanisms by which 14-3-3 paralogs regulate the centrosome cycle remain unclear. To identify the mechanisms by which 14-3-3ε regulates centrosome duplication, we altered two conserved acidic residues in the 14-3-3ε phospho-peptide-binding pocket that regulate complex formation and dissociation with the associated ligands, D127 and E134, to alanine. Altering these residues to alanine led to opposing effects on centrosome duplication; the D127A mutant inhibited centrosome duplication, whereas cells expressing the E134A mutant showed the presence of supernumerary centrosomes. We demonstrate that 14-3-3ε does not inhibit centriole duplication, as reported for 14-3-3γ, but inhibits centriole disengagement. Using a combination of pharmacological and genetic approaches, we demonstrate that 14-3-3ε inhibits the activity of Plk1 and separase [also known as separin (ESPL1)], leading to disengagement defects that ultimately lead to decreased proliferation and cell death. Our work demonstrates that different 14-3-3 paralogs regulate different steps in the centrosome cycle and that disrupting complex formation between 14-3-3ε and Plk1 or separase could be a novel therapeutic strategy in tumor cells.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Different roles of ACSL3 and ACSL4 in autophagosome formation. ACSL3和ACSL4在自噬体形成中的不同作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-07-15 Epub Date: 2025-07-29 DOI: 10.1242/jcs.263677

Shun Kato, Naoki Okada, Toshiki Ohata, Takefumi Uemura, Satoshi Waguri, Yuichi Wakana, Hiroki Inoue, Kohei Arasaki, Mitsuo Tagaya

{"title":"Different roles of ACSL3 and ACSL4 in autophagosome formation.","authors":"Shun Kato, Naoki Okada, Toshiki Ohata, Takefumi Uemura, Satoshi Waguri, Yuichi Wakana, Hiroki Inoue, Kohei Arasaki, Mitsuo Tagaya","doi":"10.1242/jcs.263677","DOIUrl":"10.1242/jcs.263677","url":null,"abstract":"Acyl-CoA synthetases (ACSLs) are a family of enzymes that convert intracellular fatty acids into acyl-CoA. A previous study has demonstrated that the yeast ACSL Faa1 (a homolog of mammalian ACSL4) is involved in autophagosome membrane elongation. In the present study, we investigated the involvement of ACSL3, a key enzyme responsible for lipid droplet formation, in autophagosome formation and compared its role with that of ACSL4. Knockdown of ACSL3 impaired starvation-induced autophagy concomitant with the formation of enlarged autophagosome-like structures negative for WIPI2, whereas its overexpression resulted in the formation of WIPI2-positive, but LC3-negative dots, under normal nutrition conditions, likely in an enzymatic activity-independent manner. In contrast, ACSL4 knockdown inhibited starvation-induced autophagosome formation, whereas its overexpression caused autophagosome formation under normal nutrition conditions. Inhibition of autophagosome formation in ACSL4-depleted cells could be rescued by ethanolamine, suggesting a deficit of phosphatidylethanolamine in ACSL4-depleted cells. These results suggest that ACSL3 and ACSL4 are involved in different stages of autophagosome formation - ACSL3 in the formation of fusion-competent autophagosomal membranes and ACSL4 in the formation of autophagosomes.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 14","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731134","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

Functional residuomics - analyzing how missense mutations impact cellular systems. 功能残基组学-分析错义突变如何影响细胞系统。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-07 DOI: 10.1242/jcs.263954

Guangshuo Ou

引用次数: 0

Adherens junctions limit septate junction length in Drosophila midgut enterocytes but are not required for polarity. 粘附连接限制了果蝇中肠肠细胞的分离连接长度，但不是极性所必需的。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-10 DOI: 10.1242/jcs.263644

Cátia A Carvalho, Mihoko A Tame, Daniel St Johnston

{"title":"Adherens junctions limit septate junction length in Drosophila midgut enterocytes but are not required for polarity.","authors":"Cátia A Carvalho, Mihoko A Tame, Daniel St Johnston","doi":"10.1242/jcs.263644","DOIUrl":"10.1242/jcs.263644","url":null,"abstract":"Adherens junctions formed by E-cadherin adhesion complexes play central roles in the organisation and apical-basal polarisation of both mammalian and insect epithelia. Here, we investigate the function of the components of the E-cadherin adhesion complex in the Drosophila midgut epithelium, which establishes polarity by a different mechanism from other fly epithelia and has an inverted junctional arrangement in which the adherens junctions lie below the septate junctions. Unlike other epithelial tissues, loss of E-cadherin, Armadillo (β-catenin) or α-catenin has no effect on the polarity or organisation of the adult midgut epithelium. This is not due to redundancy with other cadherins, as enterocytes lacking E-cadherin, N-cadherin and CadN2 still polarise normally. However, E-cadherin (shg) and armadillo mutants have expanded septate junction domains and shorter lateral domains below the septate junctions, indicating that E-cadherin adhesion complexes limit the basal extent of the septate junctions. Thus, Cadherin-mediated adhesion is dispensable for apical-basal polarity and epithelial organisation in the Drosophila midgut, in contrast to all other epithelia that have been studied so far, but it is required to define the size of the septate junctions and cell height.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Conserved biochemical activity and function of phosphatidylinositol 5-phosphate 4-kinase regulates growth and development. 磷脂酰肌醇5磷酸4激酶的保守生化活性和功能调控着生长发育。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-15 DOI: 10.1242/jcs.263881

Harini Krishnan, Suhail Muzaffar, Sanjeev Sharma, Visvanathan Ramya, Avishek Ghosh, Ramanathan Sowdhamini, Padinjat Raghu

{"title":"Conserved biochemical activity and function of phosphatidylinositol 5-phosphate 4-kinase regulates growth and development.","authors":"Harini Krishnan, Suhail Muzaffar, Sanjeev Sharma, Visvanathan Ramya, Avishek Ghosh, Ramanathan Sowdhamini, Padinjat Raghu","doi":"10.1242/jcs.263881","DOIUrl":"10.1242/jcs.263881","url":null,"abstract":"Co-ordination of function between multiple cells, mediated by hormones or growth factors, is a crucial requirement for multicellularity. Phosphoinositides, generated by lipid kinase activity, are second messengers that mediate such signalling. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) is a lipid kinase that phosphorylates phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. A comprehensive bioinformatics analysis of the tree of life, revealed that PIP4K is a metazoan-specific enzyme, but with homologues in choanoflagellates. We find that PIP4K from the sponge Amphimedon queenslandica (AqPIP4K), regarded as the earliest evolved metazoan, shows biochemical activity highly conserved with human PIP4K. Further, AqPIP4K was able to rescue the reduced cell size, growth and development of a Drosophila PIP4K mutant. These phenotypes are regulated through activity of the insulin receptor, a member of the receptor tyrosine kinase family, that is unique to metazoans. Overall, our work defines PIP4K as part of a signal transduction motif required to regulate receptor tyrosine kinase signalling for intercellular communication in the earliest forms of metazoans.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333227","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

Differential roles of cyclin-CDK1 complexes in cell migration and invasion. 细胞周期蛋白- cdk1复合物在细胞迁移和侵袭中的不同作用。

IF 3.6 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-14 DOI: 10.1242/jcs.263697

Joseph H R Hetmanski, Michael J Jones, Matthew Hartshorn, Patrick T Caswell, Matthew C Jones

引用次数: 0

A single-chain antibody-based AID2 system for conditional degradation of GFP-tagged and untagged proteins. 一种基于单链抗体的AID2系统，用于条件降解gfp标记和未标记的蛋白质。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-04 DOI: 10.1242/jcs.263961

Moutushi Islam, Takefumi Negishi, Naomi Kitamoto, Yuki Hatoyama, Kanae Gamo, Ken-Ichiro Hayashi, Masato T Kanemaki

{"title":"A single-chain antibody-based AID2 system for conditional degradation of GFP-tagged and untagged proteins.","authors":"Moutushi Islam, Takefumi Negishi, Naomi Kitamoto, Yuki Hatoyama, Kanae Gamo, Ken-Ichiro Hayashi, Masato T Kanemaki","doi":"10.1242/jcs.263961","DOIUrl":"10.1242/jcs.263961","url":null,"abstract":"Protein knockdown using an improved auxin-inducible degron (AID2) technology has proven to be a powerful tool for studying protein function. The current approach requires the fusion of target proteins with a degron tag, a process typically achieved through CRISPR knock-in. However, knock-in remains challenging in non-model organisms and humans, limiting the broader applicability of AID2. To overcome this limitation, we developed a single-chain antibody AID2 (scAb-AID2) system. This approach employs an adaptor composed of a single-chain antibody fused with a degron, which recognizes a target protein and induces rapid degradation in the presence of the inducer 5-Ph-IAA. We demonstrated that scAb-AID2, in combination with an anti-GFP nanobody, degraded GFP-fused proteins in human cells and Caenorhabditis elegans. Furthermore, we showed that endogenous p53 and H/K-RAS were conditionally degraded in cells expressing an adaptor encoding an anti-p53 nanobody and -RAS monobody, respectively, and led to aphidicolin sensitivity in cell culture and growth inhibition in mouse xenografts. This study paves the way for broader application of AID2-based target depletion in model and non-model organisms and for advancing therapeutic strategies.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248031","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

Proteasome-dependent Orc6 removal from chromatin upon S-phase entry safeguards against minichromosome maintenance complex reloading and tetraploidy. 在s期进入时，蛋白酶体依赖的Orc6从染色质上去除，防止MCM重新加载和四倍体。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-09 DOI: 10.1242/jcs.263596

Yoko Hayashi-Takanaka, Ichiro Hiratani, Tokuko Haraguchi, Yasushi Hiraoka

{"title":"Proteasome-dependent Orc6 removal from chromatin upon S-phase entry safeguards against minichromosome maintenance complex reloading and tetraploidy.","authors":"Yoko Hayashi-Takanaka, Ichiro Hiratani, Tokuko Haraguchi, Yasushi Hiraoka","doi":"10.1242/jcs.263596","DOIUrl":"10.1242/jcs.263596","url":null,"abstract":"DNA replication is tightly regulated such that it only occurs once per cell cycle, as untimely re-initiation can lead to aneuploidy, which is associated with early senescence and cancer. The pre-replication complex [comprising Orc1-Orc6, Cdc6, Cdt1 and the minichromosome maintenance complex (MCM)] is essential for the initiation of DNA replication, but the dynamics and function of Orc6 during the cell cycle remain elusive. Here, we demonstrate, using human cell lines, that Orc6 associates with chromatin during G1-phase and dissociates upon S-phase entry. The dissociation of Orc6 from chromatin is dependent on proteasome activity, and inhibition of the proteasome leads to the accumulation of chromatin-bound Orc6, which promotes abnormal MCM loading after S-phase entry without undergoing mitosis in human immortalized hTERT-RPE1 cells. Following release from proteasome inhibition, cells with elevated levels of chromatin-bound Orc6 and MCM proceed to the next replication phase as tetraploid cells. Our findings suggest that the proteasome-dependent dissociation of Orc6 after DNA replication is crucial for preventing inappropriate MCM reloading and tetraploid formation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484532","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

MitoRUSH as a tool to study the efficiency of mitochondrial import in complex I-deficient cells. MitoRUSH作为研究线粒体输入效率的工具在复杂i缺乏细胞。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-09 DOI: 10.1242/jcs.263701

Michal Wasilewski, Karthik Mohanraj, Maciej Zakrzewski, Remigiusz A Serwa, Agnieszka Chacinska

{"title":"MitoRUSH as a tool to study the efficiency of mitochondrial import in complex I-deficient cells.","authors":"Michal Wasilewski, Karthik Mohanraj, Maciej Zakrzewski, Remigiusz A Serwa, Agnieszka Chacinska","doi":"10.1242/jcs.263701","DOIUrl":"https://doi.org/10.1242/jcs.263701","url":null,"abstract":"Most mitochondrial proteins are imported through the actions of the presequence translocase of the inner membrane, the TIM23 complex, which requires energy in the form of the electrochemical potential of the inner membrane and ATP. Conversions of energy in mitochondria are disturbed in mitochondrial disorders that affect oxidative phosphorylation. Despite the widely accepted dependence of protein import into mitochondria on mitochondrial bioenergetics, effects of mitochondrial disorders on biogenesis of the mitochondrial proteome are poorly characterized. Here, we describe molecular tools that can be used to explore mitochondrial protein import in intact cells, the mitoRUSH assay, and a novel method based on labeling of nascent proteins with an amino acid analog and click chemistry. Using these orthogonal approaches, we discovered that defects in the electron transport chain and manipulating the expression of TIMM23, as well as the TIMM17A or TIMM17B paralogs, in human cells are associated with a decrease in protein import into mitochondria. We postulate that in the absence of a functional electron transfer chain, the mechanisms that support electrochemical potential of the inner membrane and ATP production are insufficient to sustain the import of proteins to mitochondria.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 13","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591328","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

MatriCom, a single-cell RNA-sequencing data mining tool to infer cell-extracellular matrix interactions. MatriCom：一个scRNA-Seq数据挖掘工具，用于推断ECM-ECM和cell-ECM通信系统。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1242/jcs.263927

Rijuta Lamba, Asia M Paguntalan, Petar B Petrov, Alexandra Naba, Valerio Izzi

{"title":"MatriCom, a single-cell RNA-sequencing data mining tool to infer cell-extracellular matrix interactions.","authors":"Rijuta Lamba, Asia M Paguntalan, Petar B Petrov, Alexandra Naba, Valerio Izzi","doi":"10.1242/jcs.263927","DOIUrl":"10.1242/jcs.263927","url":null,"abstract":"The extracellular matrix (ECM) is a complex meshwork of proteins forming the framework of all multicellular organisms. Protein interactions are critical to building and remodeling the ECM meshwork, while interactions between ECM proteins and their receptors are essential to initiate signal transduction. Here, we present MatriCom, a web application (https://matrinet.shinyapps.io/matricom) and a companion R package, devised to infer communications between ECM components and between different cell populations and the ECM from single-cell RNA-sequencing (scRNA-Seq) datasets. MatriCom relies on a unique database, MatriComDB, of over 25,000 curated interactions involving matrisome components to impute interactions from expression data. MatriCom offers the option to query user-generated or open-access datasets sourced from large sequencing efforts. MatriCom also accounts for specific rules governing ECM protein interactions. We illustrate how MatriCom can generate novel biological insights by building the first human kidney matrisome communication network. Last, applied to a panel of 46 scRNA-Seq datasets of healthy adult tissues, we demonstrate how MatriCom can shed light on the mechanisms of conservation and diversification of ECM assemblies and cell-ECM interactions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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