Molecular Biology of the Cell最新文献_第10页

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IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 DOI: 10.1091/mbc.E24-06-0244

Sandra A Murray, Erika L F Holzbaur, Mary Munson, Daniela Cimini, Timothy F Lane, Rebecca Alvania, Derek A Applewhite, Fred Chang, Elizabeth H Chen, William C Earnshaw, Chantell S Evans, Rong Li, Beata E Mierzwa, Tiffany Oliver, Verónica A Segarra, Ahna R Skop, Lesley N Weaver, David J Asai, Michael Boyce, Maria Elena Zavala, Latanya Hammonds-Odie, Jim Vigoreaux

引用次数: 0

A novel protein Moat prevents ectopic epithelial folding by limiting Bazooka/Par3-dependent adherens junctions. 一种新型蛋白质 Moat 可通过限制 Bazooka/Par3 依赖性粘连接头来防止上皮异位折叠。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-26 DOI: 10.1091/mbc.E24-04-0177

Lingkun Gu, Rolin Sauceda, Jasneet Brar, Ferdos Fessahaye, Minsang Joo, Joan Lee, Jacqueline Nguyen, Marissa Teng, Mo Weng

{"title":"A novel protein Moat prevents ectopic epithelial folding by limiting Bazooka/Par3-dependent adherens junctions.","authors":"Lingkun Gu, Rolin Sauceda, Jasneet Brar, Ferdos Fessahaye, Minsang Joo, Joan Lee, Jacqueline Nguyen, Marissa Teng, Mo Weng","doi":"10.1091/mbc.E24-04-0177","DOIUrl":"10.1091/mbc.E24-04-0177","url":null,"abstract":"Contractile myosin and cell adhesion work together to induce tissue shape changes, but how they are patterned to achieve diverse morphogenetic outcomes remains unclear. Epithelial folding occurs via apical constriction, mediated by apical contractile myosin engaged with adherens junctions, as in Drosophila ventral furrow formation. While it has been shown that a multicellular gradient of myosin contractility determines folding shape, the impact of multicellular patterning of adherens junction levels on tissue folding is unknown. We identified a novel Drosophila gene moat essential for differential apical constriction and folding behaviors across the ventral epithelium which contains both folding ventral furrow and nonfolding ectodermal anterior midgut (ectoAMG). We show that Moat functions to downregulate polarity-dependent adherens junctions through inhibiting cortical clustering of Bazooka/Par3 proteins. Such downregulation of polarity-dependent junctions is critical for establishing a myosin-dependent pattern of adherens junctions, which in turn mediates differential apical constriction in the ventral epithelium. In moat mutants, abnormally high levels of polarity-dependent junctions promote ectopic apical constriction in cells with low-level contractile myosin, resulting in expansion of infolding from ventral furrow to ectoAMG, and flattening of ventral furrow constriction gradient. Our results demonstrate that tissue-scale distribution of adhesion levels patterns apical constriction and establishes morphogenetic boundaries.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar110"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458064","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

HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis. HSPA8 抑制剂可通过加强坏死作用提高癌症化疗效果。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI: 10.1091/mbc.E24-04-0194

Erpeng Wu, Chenlu Wu, Kelong Jia, Shen'ao Zhou, Liming Sun

{"title":"HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis.","authors":"Erpeng Wu, Chenlu Wu, Kelong Jia, Shen'ao Zhou, Liming Sun","doi":"10.1091/mbc.E24-04-0194","DOIUrl":"10.1091/mbc.E24-04-0194","url":null,"abstract":"Our recent work has uncovered a novel function of HSPA8 as an amyloidase, capable of dismantling the RHIM-containing protein fibrils to suppress necroptosis. However, the impact of HSPA8 inhibitors on cancer regression via necroptosis remains unexplored. In this study, we conducted a comprehensive investigation to assess the potential of HSPA8 inhibitors in enhancing necroptosis both in vitro and in vivo. Our findings indicate that pharmacologic inhibition of HSPA8, achieved either through VER (VER-155008) targeting the nucleotide binding domain or pifithrin-μ targeting the substrate binding domain of HSPA8, significantly potentiates necroptosis induced by diverse treatments in cellular assays. These inhibitors effectively disrupt the binding of HSPA8 to the RHIM protein, impeding its regulatory function on RHIM amyloid formation. Importantly, HSPA8 inhibitors significantly enhanced cancer cell sensitivity to microtubule-targeting agents (MTAs) in vitro, while reversing chemoresistance and facilitating tumor regression by augmenting necroptosis in vivo. Our findings suggest a promising therapeutic approach to cancer through necroptosis modulation via HSPA8 targeting, particularly in combination with MTA drugs for enhanced treatment efficacy.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar108"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498444","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

Verteporfin inhibits TGF-β signaling by disrupting the Smad2/3-Smad4 interaction. Verteporfin 通过破坏 Smad2/3-Smad4 的相互作用来抑制 TGF-β 信号传导。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-02 DOI: 10.1091/mbc.E24-02-0073

Junxiu Nong, Shengqiang Shen, Fan Hong, Fan Xiao, Lingtian Meng, Pilong Li, Xiaoguang Lei, Ye-Guang Chen

{"title":"Verteporfin inhibits TGF-β signaling by disrupting the Smad2/3-Smad4 interaction.","authors":"Junxiu Nong, Shengqiang Shen, Fan Hong, Fan Xiao, Lingtian Meng, Pilong Li, Xiaoguang Lei, Ye-Guang Chen","doi":"10.1091/mbc.E24-02-0073","DOIUrl":"10.1091/mbc.E24-02-0073","url":null,"abstract":"Transforming growth factor-β (TGF-β) signaling plays a crucial role in pathogenesis, such as accelerating tissue fibrosis and promoting tumor development at the later stages of tumorigenesis by promoting epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion. Targeting TGF-β signaling is a promising therapeutic approach, but nonspecific inhibition may result in adverse effects. In this study, we focus on the Smad2/3-Smad4 complex, a key component in TGF-β signaling transduction, as a potential target for cancer therapy. Through a phase-separated condensate-aided biomolecular interaction system, we identified verteporfin (VP) as a small-molecule inhibitor that specifically targets the Smad2/3-Smad4 interaction. VP effectively disrupted the interaction between Smad2/3 and Smad4 and thereby inhibited canonical TGF-β signaling, but not the interaction between Smad1 and Smad4 in bone morphogenetic protein (BMP) signaling. Furthermore, VP exhibited inhibitory effects on TGF-β-induced EMT and cell migration. Our findings indicate a novel approach to develop protein-protein interaction inhibitors of the canonical TGF-β signaling pathway for treatments of related diseases.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar95"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861932","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

Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane. 胚芽命运决定因子通过降低细胞分裂平面的 septin 和 anillin 水平来保护胚芽前体细胞的分裂。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-02 DOI: 10.1091/mbc.E24-02-0096-T

Caroline Q Connors, Michael S Mauro, J Tristian Wiles, Andrew D Countryman, Sophia L Martin, Benjamin Lacroix, Mimi Shirasu-Hiza, Julien Dumont, Karen E Kasza, Timothy R Davies, Julie C Canman

{"title":"Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane.","authors":"Caroline Q Connors, Michael S Mauro, J Tristian Wiles, Andrew D Countryman, Sophia L Martin, Benjamin Lacroix, Mimi Shirasu-Hiza, Julien Dumont, Karen E Kasza, Timothy R Davies, Julie C Canman","doi":"10.1091/mbc.E24-02-0096-T","DOIUrl":"10.1091/mbc.E24-02-0096-T","url":null,"abstract":"Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using formincyk-1(ts) mutant Caenorhabditis elegans 4-cell embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide with greatly reduced F-actin levels at the cell division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septinUNC-59 and anillinANI-1 at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into the regulation of cytokinesis in other cell types, especially in stem cells with high potency.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar94"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861931","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

Fluorescent protein tags affect the condensation properties of a phase-separating viral protein. 荧光蛋白标签会影响相分离病毒蛋白的凝结特性。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-29 DOI: 10.1091/mbc.E24-01-0013

Russell J R Barkley, Jack C Crowley, Andrew J Brodrick, Warren R Zipfel, John S L Parker

{"title":"Fluorescent protein tags affect the condensation properties of a phase-separating viral protein.","authors":"Russell J R Barkley, Jack C Crowley, Andrew J Brodrick, Warren R Zipfel, John S L Parker","doi":"10.1091/mbc.E24-01-0013","DOIUrl":"10.1091/mbc.E24-01-0013","url":null,"abstract":"Fluorescent protein (FP) tags are extensively used to visualize and characterize the properties of biomolecular condensates despite a lack of investigation into the effects of these tags on phase separation. Here, we characterized the dynamic properties of µNS, a viral protein hypothesized to undergo phase separation and the main component of mammalian orthoreovirus viral factories. Our interest in the sequence determinants and nucleation process of µNS phase separation led us to compare the size and density of condensates formed by FP::µNS to the untagged protein. We found an FP-dependent increase in droplet size and density, which suggests that FP tags can promote µNS condensation. To further assess the effect of FP tags on µNS droplet formation, we fused FP tags to µNS mutants to show that the tags could variably induce phase separation of otherwise noncondensing proteins. By comparing fluorescent constructs with untagged µNS, we identified mNeonGreen as the least artifactual FP tag that minimally perturbed µNS condensation. These results show that FP tags can promote phase separation and that some tags are more suitable for visualizing and characterizing biomolecular condensates with minimal experimental artifacts.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar100"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161979","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

The methylome of motile cilia. 运动纤毛的甲基组

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-02 DOI: 10.1091/mbc.E24-03-0130

Stephen M King, Miho Sakato-Antoku, Ramila S Patel-King, Jeremy L Balsbaugh

{"title":"The methylome of motile cilia.","authors":"Stephen M King, Miho Sakato-Antoku, Ramila S Patel-King, Jeremy L Balsbaugh","doi":"10.1091/mbc.E24-03-0130","DOIUrl":"10.1091/mbc.E24-03-0130","url":null,"abstract":"Cilia are highly complex motile, sensory, and secretory organelles that contain perhaps 1000 or more distinct protein components, many of which are subject to various posttranslational modifications such as phosphorylation, N-terminal acetylation, and proteolytic processing. Another common modification is the addition of one or more methyl groups to the side chains of arginine and lysine residues. These tunable additions delocalize the side-chain charge, decrease hydrogen bond capacity, and increase both bulk and hydrophobicity. Methylation is usually mediated by S-adenosylmethionine (SAM)-dependent methyltransferases and reversed by demethylases. Previous studies have identified several ciliary proteins that are subject to methylation including axonemal dynein heavy chains that are modified by a cytosolic methyltransferase. Here, we have performed an extensive proteomic analysis of multiple independently derived cilia samples to assess the potential for SAM metabolism and the extent of methylation in these organelles. We find that cilia contain all the enzymes needed for generation of the SAM methyl donor and recycling of the S-adenosylhomocysteine and tetrahydrofolate byproducts. In addition, we find that at least 155 distinct ciliary proteins are methylated, in some cases at multiple sites. These data provide a comprehensive resource for studying the consequences of methyl marks on ciliary biology.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar89"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867686","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

Time-resolved cryogenic electron tomography for the study of transient cellular processes. 用于研究瞬时细胞过程的时间分辨低温电子断层扫描。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1091/mbc.E24-01-0042

Joseph Yoniles, Jacob A Summers, Kara A Zielinski, Cali Antolini, Mayura Panjalingam, Stella Lisova, Frank R Moss, Maximus Aldo Di Perna, Christopher Kupitz, Mark S Hunter, Lois Pollack, Soichi Wakatsuki, Peter D Dahlberg

{"title":"Time-resolved cryogenic electron tomography for the study of transient cellular processes.","authors":"Joseph Yoniles, Jacob A Summers, Kara A Zielinski, Cali Antolini, Mayura Panjalingam, Stella Lisova, Frank R Moss, Maximus Aldo Di Perna, Christopher Kupitz, Mark S Hunter, Lois Pollack, Soichi Wakatsuki, Peter D Dahlberg","doi":"10.1091/mbc.E24-01-0042","DOIUrl":"10.1091/mbc.E24-01-0042","url":null,"abstract":"Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare samples lends itself to time-resolved studies, which researchers have pursued for in vitro samples for decades. Here, we focus on developing a freezing apparatus for time-resolved studies in situ. The device mixes cellular samples with solution-phase stimulants before spraying them directly onto an electron microscopy grid that is transiting into cryogenic liquid ethane. By varying the flow rates of cell and stimulant solutions within the device, we can control the reaction time from tens of milliseconds to over a second before freezing. In a proof-of-principle demonstration, the freezing method is applied to a model bacterium, Caulobacter crescentus, mixed with an acidic buffer. Through cryo-ET we resolved structural changes throughout the cell, including surface-layer protein dissolution, outer membrane deformation, and cytosolic rearrangement, all within 1.5 s of reaction time. This new approach, Time-Resolved cryo-ET (TR-cryo-ET), enhances the capabilities of cryo-ET by incorporating a subsecond temporal axis and enables the visualization of induced structural changes at the molecular, organelle, or cellular level.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mr4"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876785","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

A novel noncanonical function for IRF6 in the recycling of E-cadherin. IRF6在E-cadherin循环中的一种新的非规范功能

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-29 DOI: 10.1091/mbc.E23-11-0430

Angelo Antiguas, Martine Dunnwald

引用次数: 0

GTPase activity regulates FtsZ ring positioning in Caulobacter crescentus. GTPase 活性调控新月杆菌中 FtsZ 环的定位。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-07-01 Epub Date: 2024-05-17 DOI: 10.1091/mbc.E23-09-0365

Jordan M Barrows, Barbara K Talavera-Figueroa, Isaac P Payne, Erika L Smith, Erin D Goley

{"title":"GTPase activity regulates FtsZ ring positioning in Caulobacter crescentus.","authors":"Jordan M Barrows, Barbara K Talavera-Figueroa, Isaac P Payne, Erika L Smith, Erin D Goley","doi":"10.1091/mbc.E23-09-0365","DOIUrl":"10.1091/mbc.E23-09-0365","url":null,"abstract":"Bacterial cell division is crucial for replication and requires careful coordination via proteins collectively called the divisome. The tubulin-like GTPase FtsZ is the master regulator of this process and serves to recruit downstream divisome proteins and regulate their activities. Upon assembling at mid-cell, FtsZ exhibits treadmilling motion driven by GTP binding and hydrolysis. Treadmilling is proposed to play roles in Z-ring condensation and in distribution and regulation of peptidoglycan (PG) cell wall enzymes. FtsZ polymer superstructure and dynamics are central to its function, yet their regulation is incompletely understood. We addressed these gaps in knowledge by evaluating the contribution of GTPase activity to FtsZ's function in vitro and in Caulobacter crescentus cells. We observed that a lethal mutation that abrogates FtsZ GTP hydrolysis impacts FtsZ dynamics and Z-ring positioning, but not constriction. Aberrant Z-ring positioning was due to insensitivity to the FtsZ regulator MipZ when GTPase activity is reduced. Z-ring mislocalization resulted in DNA damage, likely due to constriction over the nucleoid. Collectively, our results indicate that GTP hydrolysis serves primarily to position the Z-ring at mid-cell in Caulobacter. Proper Z-ring localization is required for effective coordination with chromosome segregation to prevent DNA damage and ensure successful cell division.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar97"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957787","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