Mona Höhler, Abel R Alcázar-Román, Katharina Schenk, Mac Pholo Aguirre-Huamani, Corinna Braun, Rafat Zrieq, Katja Mölleken, Johannes H Hegemann, Ursula Fleig
{"title":"Direct targeting of host microtubule and actin cytoskeletons by a chlamydial pathogenic effector protein.","authors":"Mona Höhler, Abel R Alcázar-Román, Katharina Schenk, Mac Pholo Aguirre-Huamani, Corinna Braun, Rafat Zrieq, Katja Mölleken, Johannes H Hegemann, Ursula Fleig","doi":"10.1242/jcs.263450","DOIUrl":"10.1242/jcs.263450","url":null,"abstract":"<p><p>To propagate within a eukaryotic cell, pathogenic bacteria hijack and remodulate host cell functions. The Gram-negative obligate intracellular Chlamydiaceae, which pose a serious threat to human and animal health, attach to host cells and inject effector proteins that reprogram host cell machineries. Members of the conserved chlamydial TarP family have been characterized as major early effectors that bind to and remodel the host actin cytoskeleton. We now describe a new function for the Chlamydia pneumoniae TarP member CPn0572, namely the ability to bind and alter the microtubule cytoskeleton. Thus, CPn0572 is unique in being the only prokaryotic protein that directly modulates both dynamic cytoskeletons of a eukaryotic cell. Ectopically expressed GFP-CPn0572 associates in a dose-independent manner with either cytoskeleton singly or simultaneously. In vitro, CPn0572 binds directly to microtubules. Expression of a microtubule-only CPn0572 variant resulted in the formation of an aberrantly thick, stabilized microtubule network. Intriguingly, during infection, secreted CPn0572 also colocalized with altered microtubules, suggesting that this protein also affects microtubule dynamics during infection. Our analysis points to a crosstalk between actin and microtubule cytoskeletons via chlamydial CPn0572.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889295","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}
Jaccoline M S Zegers, Iker Irisarri, Sophie de Vries, Jan de Vries
{"title":"Evolving circuitries in plant signaling cascades.","authors":"Jaccoline M S Zegers, Iker Irisarri, Sophie de Vries, Jan de Vries","doi":"10.1242/jcs.261712","DOIUrl":"https://doi.org/10.1242/jcs.261712","url":null,"abstract":"<p><p>Land plants are astounding processors of information; due to their sessile nature, they adjust the molecular programs that define their development and physiology in accordance with the environment in which they dwell. Transduction of the external input to the respective internal programs hinges to a large degree on molecular signaling cascades, many of which have deep evolutionary origins in the ancestors of land plants and its closest relatives, streptophyte algae. In this Review, we discuss the evolutionary history of the defining factors of streptophyte signaling cascades, circuitries that not only operate in extant land plants and streptophyte algae, but that also likely operated in their extinct algal ancestors hundreds of millions of years ago. We hope this Review offers a starting point for future studies on the evolutionary mechanisms contributing to the current diversity and complexity of plant signaling pathways, with an emphasis on recognizing potential biases.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140245","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}
Ignasi Granero-Moya, Valeria Venturini, Guillaume Belthier, Bart Groenen, Marc Molina-Jordán, Miguel González-Martín, Xavier Trepat, Jacco van Rheenen, Ion Andreu, Pere Roca-Cusachs
{"title":"Nucleocytoplasmic transport senses mechanical forces independently of cell density in cell monolayers.","authors":"Ignasi Granero-Moya, Valeria Venturini, Guillaume Belthier, Bart Groenen, Marc Molina-Jordán, Miguel González-Martín, Xavier Trepat, Jacco van Rheenen, Ion Andreu, Pere Roca-Cusachs","doi":"10.1242/jcs.262363","DOIUrl":"10.1242/jcs.262363","url":null,"abstract":"<p><p>Cells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single adhesive cells, mechanotransduction involves the transmission of force from the extracellular matrix to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators, such as YAP (also known as YAP1). However, if and how NCT is mechanosensitive in multicellular systems is unclear. Here, we characterize and use a fluorescent sensor of nucleocytoplasmic transport (Sencyt) and demonstrate that NCT responds to mechanical forces but not cell density in cell monolayers. Using monolayers of both epithelial and mesenchymal phenotype, we show that NCT is altered in response both to osmotic shocks and to the inhibition of cell contractility. Furthermore, NCT correlates with the degree of nuclear deformation measured through nuclear solidity, a shape parameter related to nuclear envelope tension. In contrast, YAP is sensitive to cell density, showing that the YAP response to cell-cell contacts is not via a mere mechanical effect of NCT. Our results demonstrate the generality of the mechanical regulation of NCT.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906713","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}
Anna Gavrilova, Astrid Boström, Nickolay Korabel, Sergei Fedotov, Gino B Poulin, Victoria J Allan
{"title":"The role of kinesin-1 in neuronal dense core vesicle transport, locomotion and lifespan regulation in C. elegans.","authors":"Anna Gavrilova, Astrid Boström, Nickolay Korabel, Sergei Fedotov, Gino B Poulin, Victoria J Allan","doi":"10.1242/jcs.262148","DOIUrl":"10.1242/jcs.262148","url":null,"abstract":"<p><p>Fast axonal transport is crucial for neuronal function and is driven by kinesins and cytoplasmic dynein. Here, we investigated the role of kinesin-1 in dense core vesicle (DCV) transport in C. elegans, using mutants in the kinesin light chains (klc-1 and klc-2) and the motor subunit (unc-116) expressing an ida-1::gfp transgene that labels DCVs. DCV transport in both directions was greatly impaired in an unc-116 mutant and had reduced velocity in a klc-2 mutant. In contrast, the speed of retrograde DCV transport was increased in a klc-1 mutant whereas anterograde transport was unaffected. We identified striking differences between the klc mutants in their effects on worm locomotion and responses to drugs affecting neuromuscular junction activity. We also determined lifespan, finding that unc-116 mutant was short-lived whereas the klc single mutant lifespan was wild type. The ida-1::gfp transgenic strain was also short-lived, but surprisingly, klc-1 and klc-2 extended the ida-1::gfp lifespan beyond that of wild type. Our findings suggest that kinesin-1 not only influences anterograde and retrograde DCV transport but is also involved in regulating lifespan and locomotion, with the two kinesin light chains playing distinct roles.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017582","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}
{"title":"Computational modeling establishes mechanotransduction as a potent modulator of the mammalian circadian clock.","authors":"Emmet A Francis, Padmini Rangamani","doi":"10.1242/jcs.261782","DOIUrl":"10.1242/jcs.261782","url":null,"abstract":"<p><p>Mechanotransduction, which is the integration of mechanical signals from the external environment of a cell to changes in intracellular signaling, governs many cellular functions. Recent studies have shown that the mechanical state of the cell is also coupled to the cellular circadian clock. To investigate possible interactions between circadian rhythms and cellular mechanotransduction, we have developed a computational model that integrates the two pathways. We postulated that translocation of the transcriptional regulators MRTF (herein referring to both MRTF-A and MRTF-B), YAP and TAZ (also known as YAP1 and WWTR1, respectively; collectively denoted YAP/TAZ) into the nucleus leads to altered expression of circadian proteins. Simulations from our model predict that lower levels of cytoskeletal activity are associated with longer circadian oscillation periods and higher oscillation amplitudes, which is consistent with recent experimental observations. Furthermore, accumulation of YAP/TAZ and MRTF in the nucleus causes circadian oscillations to decay in our model. These effects hold both at the single-cell level and within a population-level framework. Finally, we investigated the effects of mutations in YAP or lamin A, the latter of which result in a class of diseases known as laminopathies. In silico, oscillations in circadian proteins are substantially weaker in populations of cells with mutations in YAP or lamin A, suggesting that defects in mechanotransduction can disrupt the circadian clock in certain disease states; however, reducing substrate stiffness in the model restores normal oscillatory behavior, suggesting a possible compensatory mechanism. Thus, our study identifies that mechanotransduction could be a potent modulatory cue for cellular clocks and that this crosstalk can be leveraged to rescue the circadian clock in disease states.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975795","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}
{"title":"The FAM114A proteins are adaptors for the recycling of Golgi enzymes.","authors":"Lawrence G Welch, Nadine Muschalik, Sean Munro","doi":"10.1242/jcs.262160","DOIUrl":"10.1242/jcs.262160","url":null,"abstract":"<p><p>Golgi-resident enzymes remain in place while their substrates flow through from the endoplasmic reticulum to elsewhere in the cell. COPI-coated vesicles bud from the Golgi to recycle Golgi residents to earlier cisternae. Different enzymes are present in different parts of the stack, and one COPI adaptor protein, GOLPH3, acts to recruit enzymes into vesicles in part of the stack. Here, we used proximity biotinylation to identify further components of intra-Golgi vesicles and found FAM114A2, a cytosolic protein. Affinity chromatography with FAM114A2, and its paralogue FAM114A1, showed that they bind to Golgi-resident membrane proteins, with membrane-proximal basic residues in the cytoplasmic tail being sufficient for the interaction. Deletion of both proteins from U2OS cells did not cause substantial defects in Golgi function. However, a Drosophila orthologue of these proteins (CG9590/FAM114A) is also localised to the Golgi and binds directly to COPI. Drosophila mutants lacking FAM114A have defects in glycosylation of glue proteins in the salivary gland. Thus, the FAM114A proteins bind Golgi enzymes and are candidate adaptors to contribute specificity to COPI vesicle recycling in the Golgi stack.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916837","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}
Richard Bayliss, Tim Fry, Robert Mahen, Sue Shackleton, Kayoko Tanaka
{"title":"Remembering Andrew Fry (1966-2024).","authors":"Richard Bayliss, Tim Fry, Robert Mahen, Sue Shackleton, Kayoko Tanaka","doi":"10.1242/jcs.263478","DOIUrl":"https://doi.org/10.1242/jcs.263478","url":null,"abstract":"<p><p>In this article we reflect on the life and work of Andrew Fry, a renowned molecular cell biologist and a cherished member of the scientific community at the University of Leicester, UK, who passed away on 30th April 2024 at the age of 57. His groundbreaking work on the cellular mechanisms of Never in Mitosis gene-A related kinases (Neks) made an indelible mark on the field. Alongside his scientific achievements, Andrew was an exceptional mentor, a thoughtful academic leader and a dependable collaborator. To understand what motivated Andrew, we first need to look into his background.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140246","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}
Shaka X, Claire Aitken, Vedanta Mehta, Blanca Tardajos-Ayllon, Jovana Serbanovic-Canic, Jiayu Zhu, Bernadette Miao, Ellie Tzima, Paul Evans, Yun Fang, Martin A Schwartz
{"title":"Controversy in mechanotransduction - the role of endothelial cell-cell junctions in fluid shear stress sensing.","authors":"Shaka X, Claire Aitken, Vedanta Mehta, Blanca Tardajos-Ayllon, Jovana Serbanovic-Canic, Jiayu Zhu, Bernadette Miao, Ellie Tzima, Paul Evans, Yun Fang, Martin A Schwartz","doi":"10.1242/jcs.262348","DOIUrl":"10.1242/jcs.262348","url":null,"abstract":"<p><p>Fluid shear stress (FSS) from blood flow, sensed by the vascular endothelial cells (ECs) that line all blood vessels, regulates vascular development during embryogenesis, controls adult vascular physiology and determines the location of atherosclerotic plaque formation. Although a number of papers have reported a crucial role for cell-cell adhesions or adhesion receptors in these processes, a recent publication has challenged this paradigm, presenting evidence that ECs can very rapidly align in fluid flow as single cells without cell-cell contacts. To address this controversy, four independent laboratories assessed EC alignment in fluid flow across a range of EC cell types. These studies demonstrate a strict requirement for cell-cell contact in shear stress sensing over timescales consistent with previous literature and inconsistent with the newly published data.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982351","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}
Danielle B Buglak, Kathleen H M Holmes, Brian J Galletta, Nasser M Rusan
{"title":"The proximal centriole-like structure maintains nucleus-centriole architecture in sperm.","authors":"Danielle B Buglak, Kathleen H M Holmes, Brian J Galletta, Nasser M Rusan","doi":"10.1242/jcs.262311","DOIUrl":"10.1242/jcs.262311","url":null,"abstract":"<p><p>Proper connection between the sperm head and tail is critical for sperm motility and fertilization. Head-tail linkage is mediated by the head-tail coupling apparatus (HTCA), which secures the axoneme (tail) to the nucleus (head). However, the molecular architecture of the HTCA is poorly understood. Here, we use Drosophila to investigate formation and remodeling of the HTCA throughout spermiogenesis by visualizing key components of this complex. Using structured illumination microscopy, we demonstrate that key HTCA proteins Spag4 and Yuri form a 'centriole cap' that surrounds the centriole (or basal body) as it invaginates into the surface of the nucleus. As development progresses, the centriole is laterally displaced to the side of the nucleus while the HTCA expands under the nucleus, forming what we term the 'nuclear shelf'. We next show that the proximal centriole-like (PCL) structure is positioned under the nuclear shelf, functioning as a crucial stabilizer of centriole-nucleus attachment. Together, our data indicate that the HTCA is a complex, multi-point attachment site that simultaneously engages the PCL, the centriole and the nucleus to ensure proper head-tail connection during late-stage spermiogenesis.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008840","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}
Leila S Coelho-Rato, Sepideh Parvanian, Sarka Andrs Salajkova, Ohad Medalia, John E Eriksson
{"title":"Intermediate filaments at a glance.","authors":"Leila S Coelho-Rato, Sepideh Parvanian, Sarka Andrs Salajkova, Ohad Medalia, John E Eriksson","doi":"10.1242/jcs.261386","DOIUrl":"10.1242/jcs.261386","url":null,"abstract":"<p><p>Intermediate filaments (IFs) comprise a large family of versatile cytoskeletal proteins, divided into six subtypes with tissue-specific expression patterns. IFs have a wide repertoire of cellular functions, including providing structural support to cells, as well as active roles in mechanical support and signaling pathways. Consequently, defects in IFs are associated with more than 100 diseases. In this Cell Science at a Glance article, we discuss the established classes of IFs and their general features, their functions beyond structural support, and recent advances in the field. We also highlight their involvement in disease and potential use as clinical markers of pathological conditions. Finally, we provide our view on current knowledge gaps and the future directions of the IF field.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107734","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}