Molecular Biology of the Cell最新文献_第9页

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner. 乳腺癌细胞以mrtf依赖性旁分泌方式促进破骨细胞分化。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1091/mbc.E24-06-0285

Pooja Chawla, Ishani Sharma, David Gau, Ian Eder, Fangyuan Chen, Virginia Yu, Niharika Welling, David Boone, Juan Taboas, Adrian V Lee, Adriana Larregina, Deborah L Galson, Partha Roy

{"title":"Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner.","authors":"Pooja Chawla, Ishani Sharma, David Gau, Ian Eder, Fangyuan Chen, Virginia Yu, Niharika Welling, David Boone, Juan Taboas, Adrian V Lee, Adriana Larregina, Deborah L Galson, Partha Roy","doi":"10.1091/mbc.E24-06-0285","DOIUrl":"10.1091/mbc.E24-06-0285","url":null,"abstract":"Bone is a frequent site for breast cancer metastasis. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL (receptor activator for nuclear factor κB)-induced differentiation of bone marrow-derived macrophages to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that Myocardin-related transcription factor (MRTF) in breast cancer cells plays an important role in paracrine modulation of RANKL-induced OCL differentiation. This is partly attributed to MRTFs' critical role in maintaining the basal cellular expression of connective tissue growth factor (CTGF), findings that align with a strong positive correlation between CTGF expression and MRTF-A gene signature in the human disease context. Luminex analyses reveal that MRTF depletion in breast cancer cells has a broad impact on OCL-regulatory cell-secreted factors that extend beyond CTGF. Experimental metastasis studies demonstrate that MRTF depletion diminishes OCL abundance and bone colonization of breast cancer cells in vivo, suggesting that MRTF inhibition could be an effective strategy to diminish OCL formation and skeletal involvement in breast cancer. In summary, this study highlights a novel tumor-extrinsic function of MRTF relevant to breast cancer metastasis.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar8"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrophage subtypes inhibit breast cancer proliferation in culture. 巨噬细胞亚型可抑制乳腺癌的培养增殖。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1091/mbc.E24-06-0241

Sophia R S Varady, Daniel Greiner, Minna Roh-Johnson

引用次数: 0

Morphometric analysis of actin networks. 肌动蛋白网络的形态计量分析

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI: 10.1091/mbc.E24-06-0248

Oghosa H Akenuwa, Jinmo Gu, Andreas Nebenführ, Steven M Abel

{"title":"Morphometric analysis of actin networks.","authors":"Oghosa H Akenuwa, Jinmo Gu, Andreas Nebenführ, Steven M Abel","doi":"10.1091/mbc.E24-06-0248","DOIUrl":"10.1091/mbc.E24-06-0248","url":null,"abstract":"The organization of cytoskeletal elements is pivotal for coordinating intracellular transport in eukaryotic cells. Several quantitative measures based on image analysis have been proposed to characterize morphometric features of fluorescently labeled actin networks. While helpful in detecting differences in actin organization between treatments or genotypes, the accuracy of these measures could not be rigorously assessed due to a lack of ground-truth data to which they could be compared. To overcome this limitation, we utilized coarse-grained computer simulations of actin filaments and cross-linkers to generate synthetic actin networks with varying levels of bundling. We converted the simulated networks into pseudofluorescence images similar to images obtained using confocal microscopy. Using both published and novel analysis procedures, we extracted a series of morphometric parameters and benchmarked them against analogous measures based on the ground-truth actin configurations. Our analysis revealed a set of parameters that reliably reports on actin network density, orientation, ordering, and bundling. Application of these morphometric parameters to root epidermal cells of Arabidopsis thaliana revealed subtle changes in network organization between wild-type and mutant cells. This work provides robust measures that can be used to quantify features of actin networks and characterize changes in actin organization for different experimental conditions.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar146"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct peroxisome populations differentially respond to alcohol-associated hepatic injury. 不同的过氧化物酶体群对酒精相关的肝损伤有不同的反应。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-06-0252

Ramyajit Mitra, Raghabendra Adhikari, Saniya S Davis, Benita L McVicker, Pamela L Tuma

{"title":"Distinct peroxisome populations differentially respond to alcohol-associated hepatic injury.","authors":"Ramyajit Mitra, Raghabendra Adhikari, Saniya S Davis, Benita L McVicker, Pamela L Tuma","doi":"10.1091/mbc.E24-06-0252","DOIUrl":"10.1091/mbc.E24-06-0252","url":null,"abstract":"Although peroxisomes are known to oxidize ethanol, metabolize lipids, and regulate oxidative stress, they remain understudied in the context of ethanol-induced liver injury. We examined peroxisome early responses to alcohol-induced oxidative stress and lipid overload. Analysis of peroxisomes labeled with catalase, an ethanol oxidizing enzyme, or ABCD3, a fatty acid transporter, revealed that distinct peroxisome populations differentially respond to ethanol. We determined that ethanol exposure induced a reversible, time-dependent, saturable increase in functional peroxisomes labeled with either marker. This increase was due to ethanol-induced oxidative stress. In cells treated with oleic acid (to mimic fatty liver), only ABCD3-positive peroxisomes proliferated, and preferentially colocalized with lipid droplets in cells treated with oleic acid alone and/or with ethanol. In cells overexpressing the tubulin-specific acetyltransferase, αTAT1, we determined that peroxisome-lipid droplet contacts were mediated by acetylated microtubules. Peroxisome proliferation was also observed in ethanol-fed mouse and rat livers, but was absent in fibrotic mouse models of liver injury and in samples from individuals with alcohol-induced cirrhosis suggesting that alcohol exposure promotes an early hepatoprotective rise in peroxisomes that is lost as the condition progresses to fibrosis. Our studies further suggest that peroxisome proliferator-activated receptor agonists may be an effective intervention for early ethanol-associated liver disease.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar156"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicles, including large translating vesicles called midbody remnants, are released during the cell cycle. 细胞周期中会释放细胞外囊泡，包括称为中体残余的大型翻译囊泡。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E23-10-0384

Smit A Patel, Sungjin Park, Dantong Zhu, Elizabeth E Torr, Ashley-Grace Dureke, Alina McIntyre, Nadiya Muzyka, Jackson Severson, Ahna R Skop

{"title":"Extracellular vesicles, including large translating vesicles called midbody remnants, are released during the cell cycle.","authors":"Smit A Patel, Sungjin Park, Dantong Zhu, Elizabeth E Torr, Ashley-Grace Dureke, Alina McIntyre, Nadiya Muzyka, Jackson Severson, Ahna R Skop","doi":"10.1091/mbc.E23-10-0384","DOIUrl":"10.1091/mbc.E23-10-0384","url":null,"abstract":"Extracellular vesicles (EVs) play crucial roles in cell-cell communication, but the biogenesis of large EVs has remained elusive. Here, we show that the biogenesis of large EVs (>800 nm-2 µm) occurs predominantly through the completion of successful cytokinesis, and the majority of large EVs are midbody remnants (MBRs) with translation activity, and the unique marker MKLP1. Blocking the cell cycle or cytokinesis, genetically or chemically, significantly decreases MBRs and large (800 nm-2 µm), medium (500-800 nm), and small (<300 nm) EVs, suggesting that proliferative cells can also generate all sizes of EVs. The canonical EV markers including CD9, CD63, CD81 localize to the spindle midzone, midbody, and MBRs, suggesting that these markers are not specific for detecting EVs exclusively. Importantly, all commonly used EV isolation methods isolate MBRs, confounding previous EV research. Last, isolated MBRs maintain translation activity regardless of the isolation method. We propose a model for the biogenesis of EVs throughout the cell cycle and suggest that some large EVs are primarily generated from mitotic cells. The discovery of MBRs as a unique class of large, translating EVs has implications for using them as cancer diagnostic markers and for engineering them for therapeutic cargo delivery during mitosis.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar155"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporal analysis of F-actin polymerization with micropillar arrays reveals synchronization between adhesion sites. 利用微柱阵列对 F-肌动蛋白聚合的时空分析显示了粘附点之间的同步性。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI: 10.1091/mbc.E24-06-0276

Sarit Hollander, Yuanning Guo, Haguy Wolfenson, Assaf Zaritsky

引用次数: 0

DNA damage-induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells. 由 PARP 依赖性染色质重塑器 ALC1 控制的 DNA 损伤诱导的 EMT 可通过 RAD51 促进肿瘤细胞的 DNA 修复效率。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1091/mbc.E24-08-0370

Fatemeh Rajabi, Rebecca Smith, Win-Yan Liu-Bordes, Michael Schertzer, Sebastien Huet, Arturo Londoño-Vallejo

{"title":"DNA damage-induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells.","authors":"Fatemeh Rajabi, Rebecca Smith, Win-Yan Liu-Bordes, Michael Schertzer, Sebastien Huet, Arturo Londoño-Vallejo","doi":"10.1091/mbc.E24-08-0370","DOIUrl":"10.1091/mbc.E24-08-0370","url":null,"abstract":"Epithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and chemotherapeutic agents with significant implications for patients' prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT and that activation of poly (ADP-ribose) polymerase (PARP) and the PARP-dependent chromatin remodeler ALC1 (CHD1L) was required for this response. Our results suggest that this activation directly facilitates access to the chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by homologous recombination. Importantly, a clinically relevant PARP inhibitor reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response, and PARP inhibitors, providing potential insights for in cancer therapeutics.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar151"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury. 皮肤驻留巨噬细胞在稳态和组织损伤期间的钙动力学

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-09-0420

Pearl A Leon Guerrero, Jeffrey P Rasmussen, Eric Peterman

{"title":"Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury.","authors":"Pearl A Leon Guerrero, Jeffrey P Rasmussen, Eric Peterman","doi":"10.1091/mbc.E24-09-0420","DOIUrl":"10.1091/mbc.E24-09-0420","url":null,"abstract":"Immune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br26"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optical characterization of molecular interaction strength in protein condensates. 蛋白质凝聚体中分子相互作用强度的光学表征。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1091/mbc.E24-03-0128

Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus M Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck

{"title":"Optical characterization of molecular interaction strength in protein condensates.","authors":"Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus M Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck","doi":"10.1091/mbc.E24-03-0128","DOIUrl":"10.1091/mbc.E24-03-0128","url":null,"abstract":"Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques-Brillouin microscopy and quantitative phase imaging (QPI)-to address this scarcity. We establish Brillouin shift and linewidth as measures for average molecular interaction and dissipation strength, respectively, and we used QPI to obtain the protein concentration within the condensates. We monitored the response of condensates formed by fused in sarcoma (FUS) and by the low-complexity domain of hnRNPA1 (A1-LCD) to altering temperature and ion concentration. Conditions favoring phase separation increased Brillouin shift, linewidth, and protein concentration. In comparison to solidification by chemical cross-linking, the ion-dependent aging of FUS condensates had a small effect on the molecular interaction strength inside. Finally, we investigated how sequence variations of A1-LCD, that change the driving force for phase separation, alter the physical properties of the respective condensates. Our results provide a new experimental perspective on the material properties of protein condensates. Robust and quantitative experimental approaches such as the presented ones will be crucial for understanding how the physical properties of biological condensates determine their function and dysfunction.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar154"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mannose receptor (MRC1) mediates uptake of dextran by bone marrow-derived macrophages. 甘露糖受体（MRC1）介导骨髓巨噬细胞对葡聚糖的吸收。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1091/mbc.E24-08-0355

Jared Wollman, Kevin Wanniarachchi, Bijaya Pradhan, Lu Huang, Jason G Kerkvliet, Adam D Hoppe, Natalie W Thiex

{"title":"Mannose receptor (MRC1) mediates uptake of dextran by bone marrow-derived macrophages.","authors":"Jared Wollman, Kevin Wanniarachchi, Bijaya Pradhan, Lu Huang, Jason G Kerkvliet, Adam D Hoppe, Natalie W Thiex","doi":"10.1091/mbc.E24-08-0355","DOIUrl":"10.1091/mbc.E24-08-0355","url":null,"abstract":"Macrophages survey their environment using receptor-mediated endocytosis and pinocytosis. Receptor-mediated endocytosis allows internalization of specific ligands, whereas pinocytosis nonselectively internalizes extracellular fluids and solutes. CRISPR/Cas9 whole-genome screens were used to identify genes regulating constitutive and growth factor-stimulated dextran uptake in murine bone marrow-derived macrophages (BMDM). The mannose receptor c-type 1 (MRC1/CD206) was a top hit in the screen. Targeted gene disruptions of Mrc1 reduced dextran uptake but had little effect on fluid-phase uptake of Lucifer yellow. Other screen hits also differentially affected the uptake of dextran and Lucifer yellow, indicating internalization by separate mechanisms. Visualization of dextran and Lucifer yellow uptake by microscopy showed enrichment of dextran in small puncta, which was inhibitable by mannan, a ligand of MRC1. In contrast, Lucifer yellow predominantly was internalized in larger macropinosomes. In addition, IL4-treated BMDMs internalized more dextran than untreated BMDM correlating with increased MRC1 expression. Therefore, dextran is not an effective marker for pinocytosis in BMDMs since it is internalized by receptor-mediated process. Numerous genes that regulate dextran internalization in primary murine macrophages were identified in the whole-genome screens, which can inform understanding of the regulation of MRC1 expression and MRC1-mediated uptake in macrophages.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar153"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0