Journal of cell science最新文献_第3页

Human disease variants of KATNIP fail to support CILK1 activation and control of primary cilia. KATNIP的人类疾病变体不能支持CILK1的激活和对初级纤毛的控制。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-07 DOI: 10.1242/jcs.264056

Evan H Carpenter, Cheuk Ying Chu, Ana Limerick, David L Brautigan, Zheng Fu

{"title":"Human disease variants of KATNIP fail to support CILK1 activation and control of primary cilia.","authors":"Evan H Carpenter, Cheuk Ying Chu, Ana Limerick, David L Brautigan, Zheng Fu","doi":"10.1242/jcs.264056","DOIUrl":"https://doi.org/10.1242/jcs.264056","url":null,"abstract":"Pathogenic variants in KATNIP (katanin-interacting protein) are linked to Joubert syndrome, a prototypical ciliopathy. KATNIP is a scaffold protein that binds and potentiates CILK1 (ciliogenesis-associated kinase 1) activation and function to control cilia length and frequency. We previously showed that of the three predicted DUFs (Domain of Unknown Functions) in KATNIP, the DUF2 domain alone supports binding to CILK1 without activating CILK1. Here, we report three human disease variants of KATNIP with different lengths that exhibit loss of function. The longest variant of KATNIP M1474C truncated near the C-terminus binds to CILK1 but does not support the activating TDY phosphorylation in CILK1, the phosphorylation of CILK1 substrates, or the restriction of cilia length and ciliation rate. Deletion analysis of KATNIP further revealed that residues 1524-1573 encompassing predicted β-sheets and α-helix are essential for CILK1 activation and function. The results support a model where KATNIP uses separate domains to bind and to enhance activation of CILK1, enabling CILK1 function in control of cilia formation and elongation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575555","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

Transcriptional adaptation after deletion of Cdc42 in primary T cells. 原代T细胞中Cdc42缺失后的转录适应。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-04 DOI: 10.1242/jcs.263826

Adam M Rochussen, Claire Y Ma, Gillian M Griffiths

{"title":"Transcriptional adaptation after deletion of Cdc42 in primary T cells.","authors":"Adam M Rochussen, Claire Y Ma, Gillian M Griffiths","doi":"10.1242/jcs.263826","DOIUrl":"https://doi.org/10.1242/jcs.263826","url":null,"abstract":"Cdc42 is a Rho family GTPase known for its central role in cell polarity and cytoskeletal regulation. To understand the role of Cdc42 in polarised secretion from cytotoxic T lymphocytes (CTLs) we used CRISPR/Cas9 gene deletion. While Cdc42-deleted CTLs initially showed reduced secretion for up to two days after CRISPR-mediated deletion, full secretion was rapidly restored and even enhanced while CDC42 protein remained absent. In contrast, chemical inhibition of CDC42 using CASIN consistently decreased secretion in wild-type cells, but had no impact on Cdc42-deleted CTLs, confirming the specificity of this inhibitor. Comparative proteomics and transcriptomics of CTLs after Cdc42-deletion revealed transcriptional changes that could support improved T cell function including compensation via other Rho GTPases. Targeting the promoter region of Cdc42 did not trigger transcriptional adaptation, consistent with a nonsense-mediated decay mechanism of genetic compensation. Our work highlights the importance of taking orthogonal approaches to study protein function, and reveals the remarkable robustness of primary T cells to adapt to loss of an essential gene.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560245","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 adhesion plaque mediates fluid discharge and duplication of the contractile vacuole complex in Trypanosoma cruzi. 在克氏锥虫中，黏附斑块介导液体排出和收缩液泡复合体的复制。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-03 DOI: 10.1242/jcs.263810

Ingrid Augusto, Wendell Girard Dias, Alejandra Schoijet, Guillermo Daniel Alonso, Veronica Jimenez, Wanderley de Souza, Kildare Miranda

引用次数: 0

RHOA-dependent regulation of mitochondrial remodeling and cell motility in hypoxia-exposed gastric epithelial cells. 缺氧暴露的胃上皮细胞线粒体重塑和细胞运动的rhoa依赖性调节。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-02 DOI: 10.1242/jcs.263690

Aranya Pal, Prabin Bawali, Abhisek Brahma, Smruti Ranjan Rana, Rakesh Mohapatra, Debashish Chakraborty, Indrajit Poirah, Supriya Samal, Smaran Banerjee, Duane T Smoot, Hassan Ashktorab, Asima Bhattacharyya

{"title":"RHOA-dependent regulation of mitochondrial remodeling and cell motility in hypoxia-exposed gastric epithelial cells.","authors":"Aranya Pal, Prabin Bawali, Abhisek Brahma, Smruti Ranjan Rana, Rakesh Mohapatra, Debashish Chakraborty, Indrajit Poirah, Supriya Samal, Smaran Banerjee, Duane T Smoot, Hassan Ashktorab, Asima Bhattacharyya","doi":"10.1242/jcs.263690","DOIUrl":"https://doi.org/10.1242/jcs.263690","url":null,"abstract":"Mitochondrial appearance distinctively reflects cellular stress. Hypoxia, one of the most fundamental stressors, drives tumor progression, impacting mitochondrial structure and function. RAS homolog family member A (RHOA), a key regulator of cell motility, is frequently upregulated in response to hypoxia across cancers. However, its behavior under hypoxic condition in gastric cancer (GC) remains largely unexplored. Additionally, investigating the influence of RHOA in cell motility through mitochondrial reshaping is promising. Elevated RHOA level triggered mitochondrial shape-shifts from tubular to stress-associated lasso and donut, correlating with increased reactive oxygen species (ROS). However, RHOA-overexpressing cells experiencing hypoxia exhibited increased migration, despite reduced fission and ROS levels. RHO-associated coiled-coil kinase (ROCK) inhibition impaired mitochondrial shape changes, suggesting its role in mitochondrial remodeling. These results indicate a unique adaptive response to hypoxia, where RHOA upregulation increases motility and modulates mitochondrial plasticity in GC cells. In summary, RHOA-mediated mitochondrial reshaping may serve as a key regulator in tumor cell adaptation and migration in low-oxygen environments.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540347","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

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 3.3 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

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

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

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