{"title":"The novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3.","authors":"Dharma Pally, Nandini Kapoor, Alexandra Naba","doi":"10.1242/jcs.263479","DOIUrl":"10.1242/jcs.263479","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a complex meshwork comprising over 100 proteins. It serves as an adhesive substrate for cells and, hence, plays crucial roles in health and disease. We have recently identified a novel ECM protein, SNED1, and have found that it is required for neural crest cell migration and craniofacial morphogenesis during development and in breast cancer, where it is necessary for the metastatic dissemination of tumor cells. Interestingly, both processes involve the dynamic remodeling of cell-ECM adhesions via cell surface receptors. Sequence analysis revealed that SNED1 contains two amino acid motifs, RGD and LDV, known to bind integrins, the largest class of ECM receptors. We thus sought to investigate the role of SNED1 in cell adhesion. Here, we report that SNED1 mediates breast cancer and neural crest cell adhesion via its RGD motif. We further demonstrate that cell adhesion to SNED1 is mediated by the RGD integrins α5β1 and αvβ3. These findings are a first step toward identifying the signaling pathways activated downstream of the SNED1-integrin interactions guiding craniofacial morphogenesis and breast cancer metastasis.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877283","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}
{"title":"Expanding our support for the wider cell biology community.","authors":"Michael Way","doi":"10.1242/jcs.263832","DOIUrl":"https://doi.org/10.1242/jcs.263832","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046961","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}
Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey
{"title":"Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres.","authors":"Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey","doi":"10.1242/jcs.263660","DOIUrl":"10.1242/jcs.263660","url":null,"abstract":"<p><p>The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy (non-injured) human hamstring muscles for confocal microscopy (n=6) and undertook RNAscope in situ hybridisation (n=6) to gain insight into the profiles of cells and myonuclei in this region, in a fibre type manner. A marked presence of mononuclear cells was observed coating the myofibre tips (confirmed by serial block face scanning electron microscopy and cryosection immunofluorescence), with higher numbers for type I (median 29; range 16-63) than type II (16; 9-23) myofibres (P<0.05). The number of these cells expressing COL22A1 was comparable between fibre types. Myonuclear number and density gradually increased from the myofibre proper towards the tip for both fibre types (P<0.05). COL22A1 was expressed by similar proportions of myonuclei in type I (median 26%; range 13-56) and type II (19%; 3-67) myofibre tips. 70% of the COL22A1-positive nuclei in the MTJ region were myonuclei, and the remaining 30% were MTJ cells. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864229","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}
Johann Bécret, Claudia Gomez-Bravo, Camille Michaud, Ahlem Assali, Naïg A L Chenais, Izeta Kankadze, Fiona Roche, Sandrine Couvet, Coralie Fassier, Xavier Nicol
{"title":"Point contact-restricted cAMP signaling controls ephrin-A5-induced axon repulsion.","authors":"Johann Bécret, Claudia Gomez-Bravo, Camille Michaud, Ahlem Assali, Naïg A L Chenais, Izeta Kankadze, Fiona Roche, Sandrine Couvet, Coralie Fassier, Xavier Nicol","doi":"10.1242/jcs.263480","DOIUrl":"10.1242/jcs.263480","url":null,"abstract":"<p><p>Signal transduction downstream of axon guidance molecules is essential for steering developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their downstream pathways remains elusive. Subcellular compartmentation has emerged as a flexible strategy to reach such a specificity. Here, we show that point contact-restricted cAMP signals control ephrin-A5-evoked axon repulsion in vitro by modulating focal adhesion kinase (FAK; also known as PTK2) phosphorylation and the assembly and disassembly rate of point contacts. Consistent with this, preventing point contact-specific cAMP signals in developing retinal ganglion cells in vivo alters the refinement of their terminal axonal arbor in the brain. Altogether, our study identifies point contacts as a compartment containing a local cAMP signal required for ephrin-A5-dependent axon guidance and highlights the crucial role of such subcellularly restricted second messenger signals in the wiring of neuronal circuits.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949462","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}
Sarah J Bray, Stephen J Royle, Holly A Shiels, Daniel St Johnston
{"title":"The Company of Biologists: celebrating 100 years.","authors":"Sarah J Bray, Stephen J Royle, Holly A Shiels, Daniel St Johnston","doi":"10.1242/jcs.263761","DOIUrl":"https://doi.org/10.1242/jcs.263761","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931760","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}
{"title":"Stem cell expression of CXCR4 regulates tissue composition in the vomeronasal organ.","authors":"André Dietz, Katja Senf, Eva M Neuhaus","doi":"10.1242/jcs.263451","DOIUrl":"10.1242/jcs.263451","url":null,"abstract":"<p><p>The vomeronasal organ (VNO) detects signaling molecules that often prompt innate behaviors, such as aggression and reproduction. Vomeronasal sensory neurons, classified into apical and basal lineages based on receptor expression, have a limited lifespan and are continuously replaced from a common stem cell niche. Using a combination of single-cell RNA sequencing data, immunofluorescence staining and lineage tracing, we identified CXCR4 expression in proliferative stem cells and the basal neuronal lineage. Mice with a conditional knockout of Cxcr4 showed an increased number of SOX2-positive proliferative stem cells and enhanced basal neuronal lineage maturation. In addition, computational gene perturbation analysis revealed 87 transcription factors that might contribute to neurogenesis, among which was SOX2. Conditional knockout of Cxcr4 did not only disturb neuronal maturation, but also affected non-neuronal cell types, resulting in a decrease of basal lamina lining quiescent stem cells and an increase in sustentacular support cells. Together, these findings enhance our understanding how a common pool of stem cells can give rise to different cell types of the VNO, highlighting the distinct role of CXCR4 in this process.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785574","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}
Chiara Marullo, Laura Croci, Iris Giupponi, Claudia Rivoletti, Sofia Zuffetti, Barbara Bettegazzi, Ottavio Cremona, Paola Giunti, Alessandro Ambrosi, Filippo Casoni, Gian Giacomo Consalez, Franca Codazzi
{"title":"Altered Ca2+ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.","authors":"Chiara Marullo, Laura Croci, Iris Giupponi, Claudia Rivoletti, Sofia Zuffetti, Barbara Bettegazzi, Ottavio Cremona, Paola Giunti, Alessandro Ambrosi, Filippo Casoni, Gian Giacomo Consalez, Franca Codazzi","doi":"10.1242/jcs.263446","DOIUrl":"10.1242/jcs.263446","url":null,"abstract":"<p><p>Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. Although several studies have highlighted cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary cerebellar astrocytes with an RNA interference-based approach, to achieve a reduction of FXN comparable to that observed in individuals with FRDA. These FRDA-like astrocytes display some typical features of the disease, such as an increase of oxidative stress and a depletion of glutathione content. Moreover, FRDA-like astrocytes exhibit decreased Ca2+ responses to purinergic stimuli. Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, likely impairing their complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators in a Ca2+-dependent manner could affect neuronal function, contributing to neurodegeneration.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794777","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}
Heather A Baker, Jonathan P Bernardini, Veronika Csizmók, Angel Madero, Shriya Kamat, Hailey Eng, Jessica Lacoste, Faith A Yeung, Sophie Comyn, Elizabeth Hui, Gaetano Calabrese, Brian Raught, Mikko Taipale, Thibault Mayor
{"title":"The co-chaperone DNAJA2 buffers proteasomal degradation of cytosolic proteins with missense mutations.","authors":"Heather A Baker, Jonathan P Bernardini, Veronika Csizmók, Angel Madero, Shriya Kamat, Hailey Eng, Jessica Lacoste, Faith A Yeung, Sophie Comyn, Elizabeth Hui, Gaetano Calabrese, Brian Raught, Mikko Taipale, Thibault Mayor","doi":"10.1242/jcs.262019","DOIUrl":"10.1242/jcs.262019","url":null,"abstract":"<p><p>Mutations can disrupt the native function of protein by causing misfolding, which is generally handled by an intricate protein quality control network. To better understand the triaging mechanisms for misfolded cytosolic proteins, we screened a human mutation library to identify a panel of unstable mutations. The degradation of these mutated cytosolic proteins is largely dependent on the ubiquitin proteasome system. Using BioID proximity labelling, we found that the co-chaperones DNAJA1 and DNAJA2 are key interactors with one of the mutated proteins. Notably, the absence of DNAJA2 increases the turnover of the mutant but not the wild-type protein. Our work indicates that specific missense mutations in cytosolic proteins can promote enhanced interactions with molecular chaperones. Assessment of the broader panel of cytosolic mutant proteins shows that the co-chaperone DNAJA2 exhibits two distinct behaviours - acting to stabilize a wide array of cytosolic proteins, including wild-type variants, and to specifically 'buffer' some mutant proteins to reduce their turnover. Our work illustrates how distinct elements of the protein homeostasis network are utilized in the presence of a cytosolic misfolded protein.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769317","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}
{"title":"PIKFYVE inhibition induces endosome- and lysosome-derived vacuole enlargement via ammonium accumulation.","authors":"Junsuke Uwada, Hitomi Nakazawa, Takeshi Kiyoi, Takashi Yazawa, Ikunobu Muramatsu, Takayoshi Masuoka","doi":"10.1242/jcs.262236","DOIUrl":"10.1242/jcs.262236","url":null,"abstract":"<p><p>FYVE-type zinc finger-containing phosphoinositide kinase (PIKFYVE), which is essential for phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] production, is an important regulator of lysosomal homeostasis. PIKFYVE dysfunction leads to cytoplasmic vacuolization; however, the underlying mechanism remains unknown. In this study, we explored the cause of vacuole enlargement upon PIKFYVE inhibition in DU145 prostate cancer cells. Enlargement of vacuoles upon PIKFYVE inhibition required glutamine and its metabolism by glutaminases. Addition of ammonia, a metabolite of glutamine, was sufficient to enlarge vacuoles via PIKFYVE inhibition. Moreover, PIKFYVE inhibition led to intracellular ammonium accumulation. Endosome-lysosome permeabilization resulted in ammonium leakage from the cells, indicating ammonium accumulation in the endosomes and lysosomes. Ammonium accumulation and vacuole expansion were suppressed by the lysosomal lumen neutralization. It is therefore assumed that PIKFYVE inhibition interferes with the efflux of NH4+, which formed through protonation of NH3 in the lysosomal lumen, leading to osmotic swelling of vacuoles. Notably, glutamine or ammonium is required for PIKFYVE inhibition-induced suppression of lysosomal function and autophagic flux. In conclusion, this study shows that PIKFYVE inhibition disrupts lysosomal homeostasis via ammonium accumulation.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716300","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}
{"title":"Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite.","authors":"Annalise Bond, Meghan A Morrissey","doi":"10.1242/jcs.263513","DOIUrl":"https://doi.org/10.1242/jcs.263513","url":null,"abstract":"<p><p>Macrophages phagocytose, or eat, pathogens, dead cells and cancer cells. To activate phagocytosis, macrophages recognize 'eat me' signals like IgG and phosphatidylserine on the target cell surface. Macrophages must carefully adjust their phagocytic appetite to ignore non-specific or transient eat me signal exposure on healthy cells while still rapidly recognizing pathogens and debris. Depending on the context, macrophages can increase their appetite for phagocytosis, to prioritize an effective immune response, or decrease their appetite, to avoid damage to healthy tissue during homeostasis. In this Review, we discuss the biochemical and biophysical mechanisms that macrophages employ to increase or decrease their sensitivity or capacity for phagocytosis. We discuss evidence that macrophages tune their sensitivity via several mechanisms, including altering the balance of activating and inhibitory receptor expression, altering the availability of activating receptors, as well as influencing their clustering and mobility, and modulating inhibitory receptor location. We also highlight how membrane availability limits the capacity of macrophages for phagocytosis and discuss potential mechanisms to promote membrane recycling and increase phagocytic capacity. Overall, this Review highlights recent work detailing the molecular toolkit that macrophages use to alter their appetite.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921838","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}