Molecular Biology of the Cell最新文献_第9页

TSC2-mTORC1 axis regulates morphogenesis and neurological function of Gli1⁺ adult-born dentate granule cells. TSC2-mTORC1轴调控Gli1+成体天生齿状颗粒细胞的形态发生和神经功能。

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.E24-08-0366

Max Kowalczyk, Yu-Ju Lee, Wei-Hsiang Huang

{"title":"TSC2-mTORC1 axis regulates morphogenesis and neurological function of Gli1+ adult-born dentate granule cells.","authors":"Max Kowalczyk, Yu-Ju Lee, Wei-Hsiang Huang","doi":"10.1091/mbc.E24-08-0366","DOIUrl":"10.1091/mbc.E24-08-0366","url":null,"abstract":"Aberrant adult hippocampal neurogenesis is implicated in neurological and mood disorders associated with dysregulation of the mechanistic target of rapamycin (mTOR). Understanding how the mTOR pathway shapes the functional development of different subpopulations of adult-born hippocampal neural stem cells will enable insight into potential therapeutic pathways for these disorders. Here we study how loss of TSC2, a regulator of mTOR pathway and a causal gene for tuberous sclerosis complex (TSC), affects dentate gyrus granule cell morphogenesis and hippocampal-dependent function. We found that Tsc2KO mice with TSC2 specifically ablated from Gli1+ adult-born neural stem cells showed neuronal hypertrophy, reduced NEUN expression, increased dendritic arborization, premature cellular senescence, and hypervascularization of the dentate gyrus. Neurologically, Tsc2KO mice showed altered exploratory behavior, impaired spatial learning, abnormal contextual recall, and hypersensitivity to kainic acid-induced seizures. Importantly, genetic reduction of Raptor, essential for mTORC1 signaling, rebalanced mTORC1 signaling and mitigated molecular, cellular, and neurological deficits in Tsc2KO mice. This study uncovered functions of TSC2 in Gli1+ adult-born neural stem cells and highlights RAPTOR as a potential therapeutic target for reversing disease features associated with TSC2 mutations.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br1"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739895","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

Resolving the two-body problem: A postulated role for the V0 sector of the V0V1-ATPase in exosome biogenesis and multivesicular body fate. 解决两体问题：v0v1 - atp酶的V0部分在外泌体生物发生和多泡体命运中的假设作用

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2025-01-01 DOI: 10.1091/mbc.E24-09-0412

Crislyn D'Souza-Schorey, Philip D Stahl

{"title":"Resolving the two-body problem: A postulated role for the V0 sector of the V0V1-ATPase in exosome biogenesis and multivesicular body fate.","authors":"Crislyn D'Souza-Schorey, Philip D Stahl","doi":"10.1091/mbc.E24-09-0412","DOIUrl":"10.1091/mbc.E24-09-0412","url":null,"abstract":"Because the discovery of the multivesicular body (MVB) as the origin of secreted vesicles or exosomes, the question arose and still looms-what distinguishes an MVB destined for fusion with the plasma membrane (EXO-MVB) facilitating exosome release from an MVB involved in transport of content to the lysosome (LYSO-MVB). Do they have independent origins? Hence, the two-body problem. We hypothesize that a key to this conundrum is the membrane spanning V0 sector of the proton pump, V0V1-ATPase. The V0V1-ATPase participates in the acidification of intracellular compartments, although V0 can function separately from V1 and different V0 isoforms are endowed with membrane binding capabilities that allow the V0V1-ATPase to selectively localize to different endocytic compartments including early and late endosomes and lysosomes. We propose that V0, in collaboration with cholesterol and phosphoinositides, plays a central role in the early endosome as a nucleation center to direct the de novo assembly of an EXO-MVB scaffold. The EXO-MVB scaffold may play multiple roles-operating as an assembly platform, participating in membrane fission as well as providing downstream navigational queues necessary for exosome secretion. Thus, V0 may represent an influential nexus, a starting point, in exosome biogenesis.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"36 1","pages":"pe1"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869669","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

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

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