Journal of cell science最新文献_第3页

A distinct interphase microtubule state marks host cell permissiveness to Chlamydia pneumoniae entry. 明显的间期微管状态标志着宿主细胞允许肺炎衣原体进入。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265369

Katharina Schenk, Johannes Hegemann, Ursula Fleig

{"title":"A distinct interphase microtubule state marks host cell permissiveness to Chlamydia pneumoniae entry.","authors":"Katharina Schenk, Johannes Hegemann, Ursula Fleig","doi":"10.1242/jcs.265369","DOIUrl":"https://doi.org/10.1242/jcs.265369","url":null,"abstract":"Entry of intracellular pathogenic bacteria is widely considered an actin-driven process, potentially overlooking contributions of the microtubule cytoskeleton. Interphase microtubules exist in distinct states, but whether this heterogeneity influences bacterial entry is unknown. Here, using the obligate intracellular bacterium Chlamydia pneumoniae, we show that microtubules not only contribute to bacterial entry but that their pre-existing state influences host-cell permissiveness. Cells enriched in acetylated microtubules are preferentially infected, whereas detyrosinated microtubules show no such association. Taxol enhances entry, whereas selective elevation of microtubule acetylation with Tubacin does not, indicating that acetylation itself is insufficient and pointing instead to a permissive state associated with stabilized, long-lived microtubules. We next show that this relationship is reciprocal: infection induces a dose-dependent increase in microtubule acetylation that requires bacterial viability and is not reproduced by uptake of Yersinia pseudotuberculosis Invasin-coated beads, indicating that internalization alone is insufficient to trigger this response. Finally, to examine how early chlamydial proteins can alter microtubule behaviour, we assessed the effect of the secreted TarP-family actin-microtubule regulator CPn0572 on microtubule stability. In the Schizosaccharomyces pombe in vivo test system, CPn0572 promotes microtubule persistence and can act together with another chlamydial microtubule modulator to generate a combined microtubule phenotype. Together, these findings identify the pre-existing microtubule state as a determinant of Chlamydia pneumoniae entry, show that infection subsequently remodels the microtubule cytoskeleton, and demonstrate that an early chlamydial protein can directly alter microtubule behaviour.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127572","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

Insulin-stimulated phosphorylation of CLASP2 by ERK regulates microtubule plus-end binding of CLASP2 and insulin-regulated microtubule stabilization. 胰岛素刺激下ERK对CLASP2的磷酸化调节了CLASP2的微管+端结合和胰岛素调节的微管稳定。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265004

James Krantz, DeHaven McCrary, Natalie K Barker, Sara S Parker, April Mengos, Mackenzie Roman, Skylar R Batty, Atley P Moberly, Corbin Jensen, Noel Warfel, Ghassan Mouneimne, Nam Y Lee, Lawrence J Mandarino, Paul R Langlais

{"title":"Insulin-stimulated phosphorylation of CLASP2 by ERK regulates microtubule plus-end binding of CLASP2 and insulin-regulated microtubule stabilization.","authors":"James Krantz, DeHaven McCrary, Natalie K Barker, Sara S Parker, April Mengos, Mackenzie Roman, Skylar R Batty, Atley P Moberly, Corbin Jensen, Noel Warfel, Ghassan Mouneimne, Nam Y Lee, Lawrence J Mandarino, Paul R Langlais","doi":"10.1242/jcs.265004","DOIUrl":"https://doi.org/10.1242/jcs.265004","url":null,"abstract":"CLASP2, a microtubule plus-end tracking protein, exhibits changes in phosphorylation as well as localization along the microtubule in response to insulin stimulation. We report that CLASP2 is expressed in insulin target tissues such as skeletal muscle and adipose tissue and that CLASP2 protein abundance is decreased in epididymal fat of insulin resistant mice. Using a commercially available proline-directed phospho-antibody together with site-directed mutagenesis and quantitative proteomics, we establish that mouse CLASP2 (Uniprot ID Q8BRT1) undergoes insulin-stimulated phosphorylation at serines 884/893/1004/1005/1021 in 3T3-L1 adipocytes. Treatment of cells with the ERK inhibitor PD98059 inhibits the insulin-stimulated phosphorylation of CLASP2 at the proline-directed serines 893/1004/1005/1021. In vitro incubation of CLASP2 with ERK2 increases CLASP2 phosphorylation, whereas phosphorylation of a Ser884/893/1004/1005/1021Ala CLASP2 penta-mutant is decreased, indicating ERK2 is capable of directly phosphorylating CLASP2. When expressed in 3T3-L1 adipocytes, the CLASP2 penta-mutant presents significantly diminished insulin-stimulated microtubule plus-end trailing versus wildtype CLASP2. The lack of proline-directed, insulin-stimulated CLASP2 phosphorylation results in reduced insulin-induced microtubule stabilization. We introduce insulin-stimulated, proline-directed CLASP2 phosphorylation under control of the ERK pathway as a contributing factor for insulin-induced microtubule stabilization.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127589","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

Average local nucleosome motion remains nearly constant during interphase in living human cells. 在活的人类细胞间期，核小体的平均局部运动几乎保持不变。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265367

Yu Nagata, Shiori Iida, Masa A Shimazoe, Sachiko Tamura, Kako Nakazato, Kai Shimizu, Yuki Hatoyama, Masato T Kanemaki, Kazuhiro Maeshima

{"title":"Average local nucleosome motion remains nearly constant during interphase in living human cells.","authors":"Yu Nagata, Shiori Iida, Masa A Shimazoe, Sachiko Tamura, Kako Nakazato, Kai Shimizu, Yuki Hatoyama, Masato T Kanemaki, Kazuhiro Maeshima","doi":"10.1242/jcs.265367","DOIUrl":"https://doi.org/10.1242/jcs.265367","url":null,"abstract":"Dynamic chromatin behavior, which is related to chromatin accessibility, plays a critical role in various genome functions such as RNA transcription and DNA replication/repair. Previous studies using highly synchronized cells showed that average local chromatin motion, captured by single-nucleosome imaging on a subsecond time scale, remained nearly constant throughout G1, S, and G2 phases in living human cells. Here, we combined single-nucleosome imaging with Fucci cell-cycle probes to test this finding in asynchronous living human cells. Using HeLa and HCT116 cells expressing H2B-HaloTag and Fucci probes, we found that local nucleosome motion remained similar on average throughout interphase. Consistently, H3.3-Halo-labeled nucleosomes, which are enriched in Hi-C A compartments (euchromatin), also showed near-constant motion throughout interphase. Transcription inhibition increased nucleosome motion throughout interphase. Local nucleosome motion also increased following cellular perturbations, such as replication stress or DNA damage. Our findings suggest that near-constant chromatin motion supports housekeeping functions under similar physical conditions during interphase. They also suggest that cells can transiently change chromatin motion to perform ad hoc tasks in response to intra- and extracellular signals, such as DNA damage.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127621","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 truncated form of the cGMP-gated cation channel β-subunit lacking the GARP2 region transiently restores rod structure and function. 缺少GARP2区域的cgmp门控阳离子通道β-亚基的截断形式暂时恢复杆的结构和功能。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-07 DOI: 10.1242/jcs.265168

Marci L DeRamus, Zhixian Zhang, Feng He, Alex S McKeown, Jeffrey D Messinger, Timothy W Kraft, Theodore G Wensel, Steven J Pittler

{"title":"A truncated form of the cGMP-gated cation channel β-subunit lacking the GARP2 region transiently restores rod structure and function.","authors":"Marci L DeRamus, Zhixian Zhang, Feng He, Alex S McKeown, Jeffrey D Messinger, Timothy W Kraft, Theodore G Wensel, Steven J Pittler","doi":"10.1242/jcs.265168","DOIUrl":"https://doi.org/10.1242/jcs.265168","url":null,"abstract":"The cGMP-gated channel β-subunit is required for phototransduction, disc morphogenesis, and structural integrity of rod cells. Its structural role may be mediated by its GARP2 (glutamic acid rich protein) domain. To assess domain functions, we generated transgenic mice expressing a truncated protein lacking the N-terminal region on a Cngb1 null background. In these mice, light microscopy showed normal disk morphology up to 6 months, and cryo-electron tomography revealed disc-to-plasma membrane connections similar to WT. However, the truncated protein was insufficient to prevent progressive degeneration leading to photoreceptor loss by 12-14 months. Truncated protein expression levels resembled WT β-subunit levels. The truncated protein localized both to the outer segment, like WT, but also elsewhere in rods. Electroretinography showed CNG channel function was comparable to WT at 1-month and remained so up to 7.5 months postnatal when marked declines appeared. Thus, the N-terminal extension of the β-subunit is required for long-term maintenance and survival of rod photoreceptors, whereas the major structural defects observed at early ages in the knockouts cannot be attributed to loss of the CNGB1a GARP2 domain or the GARP1 and GARP2 soluble proteins.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127602","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

CelFDrive: Multimodal deep learning-assisted microscopy for automated detection of rare events. CelFDrive：用于罕见事件自动检测的多模态深度学习辅助显微镜。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-06 DOI: 10.1242/jcs.265029

Scott Brooks, Sara Toral-Pérez, Nina Pučeková, David S Corcoran, Karl Kilborn, Brian Bodensteiner, Hella Baumann, Nigel J Burroughs, Andrew D McAinsh, Till Bretschneider

{"title":"CelFDrive: Multimodal deep learning-assisted microscopy for automated detection of rare events.","authors":"Scott Brooks, Sara Toral-Pérez, Nina Pučeková, David S Corcoran, Karl Kilborn, Brian Bodensteiner, Hella Baumann, Nigel J Burroughs, Andrew D McAinsh, Till Bretschneider","doi":"10.1242/jcs.265029","DOIUrl":"https://doi.org/10.1242/jcs.265029","url":null,"abstract":"The emergence of automated microscopy has enabled the collection of large datasets of rare biological events, accelerating discovery in biology. However, most existing methods cannot be readily integrated into microscopy set-ups or are limited to a single microscope type. We present CelFDrive, a software package that automatically detects rare events of interest and automates high-resolution 3D imaging of target cells by integrating deep-learning cell classification of auxiliary low-magnification fluorescence images. We show that CelFDrive reduced the mean time required to nominate a mitotic prophase candidate for high-resolution light-sheet imaging by over 30-fold relative to manual expert selection. This approach can be used to define the order of kinetochore assembly upon nuclear envelope breakdown. The trained CelFDrive detector demonstrated transferability by retaining mitotic-cell detection capability in an independently generated dataset using a different cell line, DNA marker and imaging setup. As datasets grow and models improve, CelFDrive offers a clear path toward intelligent imaging systems that not only accelerate data collection but also fundamentally enhance how biological questions are explored.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110236","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

Higher frequency of homologous chromosome pairing in adult endothelial cells as compared to neonatal endothelial cells. 与新生儿内皮细胞相比，成人内皮细胞的同源染色体配对频率更高。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-06 DOI: 10.1242/jcs.264668

Jemery Morales, Omar Akhtar, Gabriel Quintero Plancarte, Lisa Hua

{"title":"Higher frequency of homologous chromosome pairing in adult endothelial cells as compared to neonatal endothelial cells.","authors":"Jemery Morales, Omar Akhtar, Gabriel Quintero Plancarte, Lisa Hua","doi":"10.1242/jcs.264668","DOIUrl":"10.1242/jcs.264668","url":null,"abstract":"Homologous chromosomes are spatially segregated, or antipaired, in neonatal human endothelial cells at metaphase/anaphase, which may help prevent abnormal recombination. However, it is unclear if this antipairing persists in adult endothelial cells. To test whether the antipairing, or one homolog per nuclear hemisphere motif, is conserved in adult endothelial cells, we examined human aortic endothelial cells at metaphase. Using ImmunoFISH and high-resolution confocal microscopy to visualize the chromosomes and centrosomes, we found that small homologous chromosomes 13, 15, 17, 19, 21, 22, and the sex chromosomes, XY, exhibit a loss of spatial segregation in human adult aortic endothelial cells. In addition, fewer adult endothelial cells showed segregation for the larger chromosomes 1, 4, and XX, as compared to neonatal endothelial cells. Notably, we observed a higher frequency of abnormal pairing in both small and large chromosomes in adult aortic endothelial cells as compared to neonatal umbilical vein endothelial cells. These findings suggest that mechanisms governing chromosome antipairing may decline with aortic endothelial cell age.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110299","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

CRB3 and ARP2/3 regulate cell biomechanical properties to set epithelial monolayers for collective movement. CRB3和ARP2/3调节细胞的生物力学特性，设置上皮单分子层进行集体运动。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-06 DOI: 10.1242/jcs.263667

Dominique Massey-Harroche, Vito Conte, Niels Gouirand, Juna Como, Michäel Sebbagh, André Le Bivic, Elsa Bazellières

{"title":"CRB3 and ARP2/3 regulate cell biomechanical properties to set epithelial monolayers for collective movement.","authors":"Dominique Massey-Harroche, Vito Conte, Niels Gouirand, Juna Como, Michäel Sebbagh, André Le Bivic, Elsa Bazellières","doi":"10.1242/jcs.263667","DOIUrl":"https://doi.org/10.1242/jcs.263667","url":null,"abstract":"Several cellular processes during morphogenesis, tissue healing or cancer progression involve collective cell migration. To set the cells for motion, there is an initial breaking of organization of the epithelial tissue that modifies the epithelial phenotype and axis of polarity. During this process, the actin cytoskeleton and cellular junctions are extensively remodeled correlating with the buildup of mechanical forces. As the collective migration proceeds, mechanical forces generated by the actin cytoskeleton align with the direction of migration ensuring an organized and efficient collective cell behavior, but how forces are regulated during the breaking of symmetry at the onset of collective motion remains an unaddressed question. It is known that the polarity complex CRB3/PALS1/PATJ, and in particular, CRB3 regulates the organization of the actin cytoskeleton associated to the apical domain thus pointing at a potential role of CRB3 in controlling mechanical forces. Whether and how CRB3 influences epithelial biomechanics during collective cell motion remains, however, largely unexplored. Here, we systematically combine mechanical and molecular analyses to show that CRB3 regulates the biomechanical properties of collective epithelial cells during the initial breaking of epithelial tissue organization. CRB3 interacts with ARP2/3 and controls the remodeling of actin via the modulation of the Rho-/Rac-GTPase balance, and more precisely by acting upstream of the activation of Rac1. Taken together, our results identified CRB3, a polarity protein, as a regulator of epithelial monolayer mechanics during collective cell motion.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110270","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

Tubulin polyglutamylation modulates Golgi morphodynamics and neurite branching during neuronal morphogenesis. 小管蛋白多谷氨酰化在神经元形态发生过程中调节高尔基体形态动力学和神经突分支。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-02 DOI: 10.1242/jcs.264960

Chih-Hsuan Hsu, Alexander Josiah Kinrade, Sarah Cohen

{"title":"Tubulin polyglutamylation modulates Golgi morphodynamics and neurite branching during neuronal morphogenesis.","authors":"Chih-Hsuan Hsu, Alexander Josiah Kinrade, Sarah Cohen","doi":"10.1242/jcs.264960","DOIUrl":"https://doi.org/10.1242/jcs.264960","url":null,"abstract":"Neurons establish functional networks through morphological remodeling during neuronal differentiation. Microtubule polyglutamylation is a key microtubule post-translational modification that is highly enriched during this process and plays an important role in differentiation. However, how remodeling of organelle features such as morphology, distribution and interactions depends on tubulin polyglutamylation during neuronal differentiation remain unclear. Here, we employed multispectral imaging combined with quantitative 3D organelle analysis to comprehensively profile eight organelles simultaneously in human induced pluripotent stem cell-derived neurons. We discovered that depletion of tubulin polyglutamylation induces pronounced alterations in somatic Golgi morphology and associated organelle interactions. In addition, Golgi-derived compartments in proximal neurites exhibited altered morphology and dynamics, namely decreased anterograde transport together with less efficient movement. These changes were accompanied by increased neurite branching and tortuosity. Together, our findings reveal a previously unrecognized role for tubulin polyglutamylation in coordinating organelle organization with neurite architecture, providing a mechanistic link between tubulin post-translational modification, Golgi morphology, dynamics, and neuronal morphogenesis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109823","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

Distinct roles for TANGO1S domains in maintaining ER-Golgi architecture. TANGO1S域在维护er -高尔基体系结构中的不同角色。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-02 DOI: 10.1242/jcs.265001

Elizabeth A Lawrence, Lorna Hodgson, Judith Mantell, M Esther Prada-Sanchez, Chrissy L Hammond, David J Stephens, Nicola L Stevenson

{"title":"Distinct roles for TANGO1S domains in maintaining ER-Golgi architecture.","authors":"Elizabeth A Lawrence, Lorna Hodgson, Judith Mantell, M Esther Prada-Sanchez, Chrissy L Hammond, David J Stephens, Nicola L Stevenson","doi":"10.1242/jcs.265001","DOIUrl":"https://doi.org/10.1242/jcs.265001","url":null,"abstract":"The endoplasmic reticulum (ER)-Golgi interface is a dynamic trafficking hub maintained in part by TANGO1, a scaffolding protein that coordinates proteins and membranes at ER exit sites (ERES). TANGO1 has two isoforms: TANGO1L, which has a lumenal SH3 domain, and TANGO1S, which lacks this domain but retains the transmembrane and cytoplasmic coiled-coil (CC), TEER, and PRD domains common to both forms. We showed previously that loss of both isoforms disrupts ER-Golgi organization more severely than TANGO1L loss alone, indicating TANGO1S is functional and can compensate. Here we dissect the role of each TANGO1 cytoplasmic domain in maintaining secretory pathway organisation by expressing TANGO1S domain-deletion mutants in TANGO1L-/S- knockout cells. We show that TANGO1 loss causes cis-Golgi vesiculation that cannot be rescued by TANGO1S. TANGO1S re-expression also failed to rescue COPII and Sec16 recruitment in this cell line. Meanwhile, the TEER domain is essential for the organisation of the ER, and the TEER, CC2 and PRD domain are required for a defined ERGIC. This study represents an advance towards a domain-level resolution of TANGO1S function.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110268","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

Mechanotransduction through LFA-1 controls upstream migration in the KG-1a stem cell line. 通过LFA-1的机械转导控制KG-1a干细胞系的上游迁移。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-10-01 Epub Date: 2026-10-14 DOI: 10.1242/jcs.265036

Ai Mochida, Emily Valerio, Janis K Burkhardt, Daniel A Hammer

{"title":"Mechanotransduction through LFA-1 controls upstream migration in the KG-1a stem cell line.","authors":"Ai Mochida, Emily Valerio, Janis K Burkhardt, Daniel A Hammer","doi":"10.1242/jcs.265036","DOIUrl":"https://doi.org/10.1242/jcs.265036","url":null,"abstract":"Immune cell recruitment into tissues requires cells to migrate on the endothelium while overcoming shear forces. Many extravasating cells, including T lymphocytes and hematopoietic stem cells, migrate upstream against the direction of shear flow on ICAM-1. Upstream migration has been shown to depend on intracellular signaling through Crk family adaptor proteins following engagement of lymphocyte function-associated antigen-1 (LFA-1). Because upstream migration is an important illustration of leukocyte mechanotransduction, we sought to identify key intracellular regulators of upstream migration using CRISPR/Cas9 gene editing and the KG-1a stem cell line. We made targeted deletions of molecules that function downstream of LFA-1 to regulate actin polymerization, link integrin signaling to the actin cytoskeleton, or form scaffolding complexes with Crk proteins. We found that CrkL, CasL (also known as HEF1 or NEDD9), L-plastin (LCP1) and RIAM (APBB1IP) are crucial for dynamic F-actin-rich lamellipodia and upstream migration. Although WASP (WAS), Hem1 (NCKAP1L), EVL and vinculin were found to be dispensable for upstream migration, pan-formin inhibition with SMIFH2 revealed a role for formins in upstream migration. This study illustrates the role of LFA-1 mechanotransduction in driving F-actin assembly at the leading edge to drive upstream migration.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 19","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182046","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