European journal of cell biology最新文献

{"title":"Kinase activity of histone chaperone APLF maintains steady state of centrosomes in mouse embryonic stem cells","authors":"Sruthy Manuraj Rajam ,&nbsp;Pallavi Chinnu Varghese ,&nbsp;Mayur Balkrishna Shirude ,&nbsp;Khaja Mohieddin Syed ,&nbsp;Anjali Devarajan ,&nbsp;Kathiresan Natarajan ,&nbsp;Debasree Dutta","doi":"10.1016/j.ejcb.2024.151439","DOIUrl":"10.1016/j.ejcb.2024.151439","url":null,"abstract":"<div><p>Our recent studies revealed the role of mouse Aprataxin PNK-like Factor (APLF) in development. Nevertheless, the comprehensive characterization of mouse APLF remains entirely unexplored. Based on domain deletion studies, here we report that mouse APLF's Acidic Domain and Fork Head Associated (FHA) domain can chaperone histones and repair DNA like the respective human orthologs. Immunofluorescence studies in mouse embryonic stem cells showed APLF co-localized with γ-tubulin within and around the centrosomes and govern the number and integrity of centrosomes via PLK4 phosphorylation. Enzymatic analysis established mouse APLF as a kinase. Docking studies identified three putative ATP binding sites within the FHA domain. Site-directed mutagenesis showed that R37 residue within the FHA domain is indispensable for the kinase activity of APLF thereby regulating the centrosome number. These findings might assist us comprehend APLF in different pathological and developmental conditions and reveal non-canonical kinase activity of proteins harbouring FHA domains that might impact multiple cellular processes.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151439"},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000566/pdfft?md5=f9b67a2e63edf7473ac1ba067f0da878&pid=1-s2.0-S0171933524000566-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537789","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":"Alterations of receptors and insulin-like growth factor binding proteins in senescent cells","authors":"Julia Matuszewska ,&nbsp;Adrianna Krawiec ,&nbsp;Artur Radziemski ,&nbsp;Paweł Uruski ,&nbsp;Andrzej Tykarski ,&nbsp;Justyna Mikuła-Pietrasik ,&nbsp;Krzysztof Książek","doi":"10.1016/j.ejcb.2024.151438","DOIUrl":"10.1016/j.ejcb.2024.151438","url":null,"abstract":"<div><p>The knowledge about cellular senescence expands dynamically, providing more and more conclusive evidence of its triggers, mechanisms, and consequences. Senescence-associated secretory phenotype (SASP), one of the most important functional traits of senescent cells, is responsible for a large extent of their context-dependent activity. Both SASP’s components and signaling pathways are well-defined. A literature review shows, however, that a relatively underinvestigated aspect of senescent cell autocrine and paracrine activity is the change in the production of proteins responsible for the reception and transmission of SASP signals, i.e., receptors and binding proteins. For this reason, we present in this article the current state of knowledge regarding senescence-associated changes in cellular receptors and insulin-like growth factor binding proteins. We also discuss the role of these alterations in senescence induction and maintenance, pro-cancerogenic effects of senescent cells, and aging-related structural and functional malfunctions.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151438"},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000554/pdfft?md5=686a49fea7150fa4545825733a880e8a&pid=1-s2.0-S0171933524000554-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467025","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":"Osteogenic differentiation of periodontal ligament fibroblasts inhibits osteoclast formation","authors":"Caya M. Prins ,&nbsp;Merve Ceylan ,&nbsp;Jolanda M.A. Hogervorst ,&nbsp;Ineke D.C. Jansen ,&nbsp;Irene M. Schimmel ,&nbsp;Ton Schoenmaker ,&nbsp;Teun J. de Vries","doi":"10.1016/j.ejcb.2024.151440","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151440","url":null,"abstract":"<div><p>One of the deficits of knowledge on bone remodelling, is to what extent cells that are driven towards osteogenic differentiation can contribute to osteoclast formation. The periodontal ligament fibroblast (PdLFs) is an ideal model to study this, since they play a role in osteogenesis, and can also orchestrate osteoclastogenesis.when co-cultured with a source of osteoclast-precursor such as peripheral blood mononuclear cells (PBMCs). Here, the osteogenic differentiation of PdLFs and the effects of this process on the formation of osteoclasts were investigated. PdLFs were obtained from extracted teeth and exposed to osteogenic medium for 0, 7, 14, or 21 out of 21 days. After this 21-day culturing period, the cells were co-cultured with peripheral blood mononuclear cells (PBMCs) for an additional 21 days to study osteoclast formation. Alkaline phosphatase (ALP) activity, calcium concentration, and gene expression of osteogenic markers were assessed at day 21 to evaluate the different stages of osteogenic differentiation. Alizarin red staining and scanning electron microscopy were used to visualise mineralisation. Tartrate-resistant acid phosphatase (TRAcP) activity, TRAcP staining, multinuclearity, the expression of osteoclastogenesis-related genes, and TNF-α and IL-1β protein levels were assessed to evaluate osteoclastogenesis. The osteogenesis assays revealed that PdLFs became more differentiated as they were exposed to osteogenic medium for a longer period of time. Mineralisation by these osteogenic cells increased with the progression of differentiation. Culturing PdLFs in osteogenic medium before co-culturing them with PMBCs led to a significant decrease in osteoclast formation. qPCR revealed significantly lower <em>DCSTAMP</em> expression in cultures that had been supplemented with osteogenic medium. Protein levels of osteoclastogenesis stimulator TNF-α were also lower in these cultures. The present study shows that the osteogenic differentiation of PdLFs reduces the osteoclastogenic potential of these cells. Immature cells of the osteoblastic lineage may facilitate osteoclastogenesis, whereas mature mineralising cells may suppress the formation of osteoclasts. Therefore, mature and immature osteogenic cells may have different roles in maintaining bone homeostasis.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151440"},"PeriodicalIF":4.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000578/pdfft?md5=1eb1d93c5abf808f2cc5b4e0e2a279c6&pid=1-s2.0-S0171933524000578-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485430","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":"Sperm chromatin: Evaluation, epigenetic signatures and relevance for embryo development and assisted reproductive technology outcomes","authors":"Pauline Balder ,&nbsp;Celine Jones ,&nbsp;Kevin Coward ,&nbsp;Marc Yeste","doi":"10.1016/j.ejcb.2024.151429","DOIUrl":"10.1016/j.ejcb.2024.151429","url":null,"abstract":"<div><p>Sperm chromatin is distinct from somatic cell chromatin, as a result of extensive remodeling during the final stages of spermatogenesis. In this process, the majority of histones is replaced with protamines. The chromatin is consequently highly condensed and inert, which facilitates protection of the DNA. The sperm epigenomic landscape is shaped by histone retention, histone and protamine modification, DNA methylation, and RNAs. In recent years, sperm chromatin integrity and its epigenetic marks have been increasingly studied, and the constitution of sperm chromatin is steadily being uncovered. This growing body of research prompts assessment of the frequently overlooked involvement of sperm in fertility and embryonic development. Moreover, numerous endogenous and exogenous factors are known to affect sperm chromatin, which may in turn impact the reproductive success. Concerns have been raised about the effects of assisted reproductive technology (ART) on the sperm epigenome, embryonic development and offspring health. This review examines the structure and epigenetic signatures of sperm chromatin in the context of fertility and early embryonic development. Additionally, sperm chromatin evaluation and causes of aberrant integrity are outlined. Building on the knowledge discussed in the current review, future research should aim to elucidate the intricate relationship between all aspects of sperm chromatin and embryo development. This could lead to the uncovering of new targets for treating infertility, as well as the acquisition of much needed insights into the possible reciprocal association between ART and sperm chromatin integrity.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151429"},"PeriodicalIF":4.5,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000463/pdfft?md5=b59b83b2b7f9a4a42708cb232813d86c&pid=1-s2.0-S0171933524000463-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141400730","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 CCTδ subunit of the molecular chaperone CCT is required for correct localisation of p150Glued to spindle poles during mitosis","authors":"Carmen M. Córdoba-Beldad,&nbsp;Julie Grantham","doi":"10.1016/j.ejcb.2024.151430","DOIUrl":"10.1016/j.ejcb.2024.151430","url":null,"abstract":"<div><p>Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index. Mitotic defects, such as unaligned chromosomes occur when CCTδ is depleted, concurrent with a reduction in spindle pole-localised p150^Glued, a component of the dynactin complex and a binding partner of monomeric CCTδ. In CCTδ-depleted cells, changes in the elution profile of p150^Glued are observed consistent with altered conformations and or assembly states with the dynactin complex. Addition of monomeric CCTδ, in the form of GFP-CCTδ, restores correct p150^Glued localisation to the spindle poles and rescues the mitotic segregation defects that occur when CCTδ is depleted. This study demonstrates a requirement for CCTδ in its monomeric form for correct chromosome segregation via a mechanism that promotes the correct localisation of p150^Glued, thus revealing further complexities to the interplay between CCT, tubulin folding and microtubule dynamics.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151430"},"PeriodicalIF":6.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000475/pdfft?md5=b46adc17cb28a7c1e9e5f3c7d7ba6f8f&pid=1-s2.0-S0171933524000475-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141394691","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 mechanical mechanism of angiotensin II induced activation of hepatic stellate cells promoting portal hypertension","authors":"Yiheng Zhang ,&nbsp;Mulan Xing ,&nbsp;Fansheng Meng ,&nbsp;Ling Zhu ,&nbsp;Qingchuan Huang ,&nbsp;Tianle Ma ,&nbsp;Huihua Fang ,&nbsp;Xujing Gu ,&nbsp;Suzhou Huang ,&nbsp;Xinyu Wu ,&nbsp;Gaohong Lv ,&nbsp;Jun Guo ,&nbsp;Li Wu ,&nbsp;Xin Liu ,&nbsp;Zhipeng Chen","doi":"10.1016/j.ejcb.2024.151427","DOIUrl":"10.1016/j.ejcb.2024.151427","url":null,"abstract":"<div><p>In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca²⁺ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151427"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017193352400044X/pdfft?md5=d0ffa0347f368a5f5bda649cec39f952&pid=1-s2.0-S017193352400044X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183738","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":"Targeting F-actin stress fibers to suppress the dedifferentiated phenotype in chondrocytes","authors":"Mandy M. Schofield ,&nbsp;Alissa T. Rzepski ,&nbsp;Stephanie Richardson-Solorzano ,&nbsp;Jonah Hammerstedt ,&nbsp;Sohan Shah ,&nbsp;Chloe E. Mirack ,&nbsp;Marin Herrick ,&nbsp;Justin Parreno","doi":"10.1016/j.ejcb.2024.151424","DOIUrl":"10.1016/j.ejcb.2024.151424","url":null,"abstract":"<div><p>Actin is a central mediator of the chondrocyte phenotype. Monolayer expansion of articular chondrocytes on tissue culture polystyrene, for cell-based repair therapies, leads to chondrocyte dedifferentiation. During dedifferentiation, chondrocytes spread and filamentous (F-)actin reorganizes from a cortical to a stress fiber arrangement causing a reduction in cartilage matrix expression and an increase in fibroblastic matrix and contractile molecule expression. While the downstream mechanisms regulating chondrocyte molecular expression by alterations in F-actin organization have become elucidated, the critical upstream regulators of F-actin networks in chondrocytes are not completely known. Tropomyosin (TPM) and the RhoGTPases are known regulators of F-actin networks. The main purpose of this study is to elucidate the regulation of passaged chondrocyte F-actin stress fiber networks and cell phenotype by the specific TPM, TPM3.1, and the RhoGTPase, CDC42. Our results demonstrated that TPM3.1 associates with cortical F-actin and stress fiber F-actin in primary and passaged chondrocytes, respectively. In passaged cells, we found that pharmacological TPM3.1 inhibition or siRNA knockdown causes F-actin reorganization from stress fibers back to cortical F-actin and causes an increase in G/F-actin. CDC42 inhibition also causes formation of cortical F-actin. However, pharmacological CDC42 inhibition, but not TPM3.1 inhibition, leads to the re-association of TPM3.1 with cortical F-actin. Both TPM3.1 and CDC42 inhibition, as well as TPM3.1 knockdown, reduces nuclear localization of myocardin related transcription factor, which suppresses dedifferentiated molecule expression. We confirmed that TPM3.1 or CDC42 inhibition partially redifferentiates passaged cells by reducing fibroblast matrix and contractile expression, and increasing chondrogenic SOX9 expression. A further understanding on the regulation of F-actin in passaged cells may lead into new insights to stimulate cartilage matrix expression in cells for regenerative therapies.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151424"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000414/pdfft?md5=b34dc391c5f6ee6137c475343b9955d5&pid=1-s2.0-S0171933524000414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186171","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":"Membrane localization of actin filaments stabilizes giant unilamellar vesicles against external deforming forces","authors":"Andreas Fink ,&nbsp;Sunnatullo Fazliev ,&nbsp;Tobias Abele ,&nbsp;Joachim P. Spatz ,&nbsp;Kerstin Göpfrich ,&nbsp;Elisabetta Ada Cavalcanti-Adam","doi":"10.1016/j.ejcb.2024.151428","DOIUrl":"10.1016/j.ejcb.2024.151428","url":null,"abstract":"<div><p>Actin organization is crucial for establishing cell polarity, which influences processes such as directed cell motility and division. Despite its critical role in living organisms, achieving similar polarity in synthetic cells remains challenging. In this study, we employ a bottom-up approach to investigate how molecular crowders facilitate the formation of cortex-like actin networks and how these networks localize and organize based on membrane shape. Using giant unilamellar vesicles (GUVs) as models for cell membranes, we show that actin filaments can arrange along the membrane to form cortex-like structures. Notably, this organization is achieved using only actin and crowders as a minimal set of components. We utilize surface micropatterning to examine actin filament organization in deformed GUVs adhered to various pattern shapes. Our findings indicate that at the periphery of spherical GUVs, actin bundles align along the membrane. However, in highly curved regions of adhered GUVs, actin bundles avoid crossing the highly curved edges perpendicular to the adhesion site and instead remain in the lower curved regions by aligning parallel to the micropatterned surface. Furthermore, the actin bundles increase the stiffness of the GUVs, effectively counteracting strong deformations when GUVs adhere to micropatterns. This finding is corroborated by real-time deformability cytometry on GUVs with synthetic actin cortices. By precisely manipulating the shape of GUVs, our study provides a minimal system to investigate the interplay between actin structures and the membrane. Our findings provide insights into the spatial organization of actin structures within crowded environments, specifically inside GUVs that resemble the size and shape of cells. This study advances our understanding of actin network organization and functionality within cell-sized compartments.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151428"},"PeriodicalIF":6.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000451/pdfft?md5=50716cf9eab95bdd5eeed968c7b7c752&pid=1-s2.0-S0171933524000451-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278415","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 TRIP6/LATS1 complex constitutes the tension sensor of α-catenin/vinculin at both bicellular and tricellular junctions","authors":"Lin Xie ,&nbsp;Gangyun Wu ,&nbsp;Xiayu Liu ,&nbsp;Xiufen Duan ,&nbsp;Kaiyao Zhou ,&nbsp;Hua Li ,&nbsp;Wenxiu Ning","doi":"10.1016/j.ejcb.2024.151426","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151426","url":null,"abstract":"<div><p>Cell-cell mechanotransduction regulates tissue development and homeostasis. α-catenin, the core component of adherens junctions, functions as a tension sensor and transducer by recruiting vinculin and transducing signals that influence cell behaviors. α-catenin/vinculin complex-mediated mechanotransduction regulates multiple pathways, such as Hippo pathway. However, their associations with the α-catenin-based tension sensors at cell junctions are still not fully addressed. Here, we uncovered the TRIP6/LATS1 complex co-localizes with α-catenin/vinculin at both bicellular junctions (BCJs) and tricellular junctions (TCJs). The localization of TRIP6/LATS1 complex to both TCJs and BCJs requires ROCK1 and α-catenin. Treatment by cytochalasin B, Y-27632 and blebbistatin all impaired the BCJ and TCJ junctional localization of TRIP6/LATS1, indicating that the junctional localization of TRIP6/LATS1 is mechanosensitive. The α-catenin/vinculin/TRIP6/LATS1 complex strongly localized to TCJs and exhibited a discontinuous button-like pattern on BCJs. Additionally, we developed and validated an α-catenin/vinculin BiFC-based mechanosensor that co-localizes with TRIP6/LATS1 at BCJs and TCJs. The mechanosensor exhibited a discontinuous distribution and motile signals at BCJs. Overall, our study revealed that TRIP6 and LATS1 are novel compositions of the tension sensor, together with the core complex of α-catenin/vinculin, at both the BCJs and TCJs.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151426"},"PeriodicalIF":6.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000438/pdfft?md5=4f9e2123cd493723f7610560642cb990&pid=1-s2.0-S0171933524000438-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156316","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":"Multicomponent depolymerization of actin filament pointed ends by cofilin and cyclase-associated protein depends upon filament age","authors":"Ekram M. Towsif,&nbsp;Blake Andrew Miller,&nbsp;Heidi Ulrichs,&nbsp;Shashank Shekhar","doi":"10.1016/j.ejcb.2024.151423","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151423","url":null,"abstract":"<div><p>Intracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by “aging” of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus “treadmill” through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-P_i actin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-P_i filaments. Interestingly, the maximal rates of ADP-P_i filament depolymerization by CAP and cofilin together remain approximately 20–40 times lower than for ADP filaments. Further, we find that the promotion of ADP-P_i pointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of P_i release in the aging process.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151423"},"PeriodicalIF":6.6,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000402/pdfft?md5=ec5671fe282b4839686c7c4f655ec2a6&pid=1-s2.0-S0171933524000402-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141095317","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}