Molecular Biology of the Cell最新文献

Zelda is dispensable for Drosophila melanogaster histone gene regulation.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-11 DOI: 10.1091/mbc.E24-01-0028

Tommy O'Haren, Tsutomu Aoki, Leila E Rieder

引用次数: 0

TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in Saccharomyces cerevisiae.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-11 DOI: 10.1091/mbc.E24-04-0147

Sarah R Chadwick, Samuel Stack-Couture, Matthew D Berg, Sonja Di Gregorio, Bryan Lung, Julie Genereaux, Robyn D Moir, Christopher J Brandl, Ian M Willis, Erik L Snapp, Patrick Lajoie

{"title":"TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in Saccharomyces cerevisiae.","authors":"Sarah R Chadwick, Samuel Stack-Couture, Matthew D Berg, Sonja Di Gregorio, Bryan Lung, Julie Genereaux, Robyn D Moir, Christopher J Brandl, Ian M Willis, Erik L Snapp, Patrick Lajoie","doi":"10.1091/mbc.E24-04-0147","DOIUrl":"https://doi.org/10.1091/mbc.E24-04-0147","url":null,"abstract":"Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA), has been described as a chemical chaperone. While promising in models of protein folding diseases, TUDCA's mechanism of action remains unclear. Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or over-expression of a misfolded mutant secretory protein. Neither pretreatment with or delayed addition of TUDCA conferred protection against Tm. Importantly, attenuation of Tm-induced toxicity required TUDCA's critical micelle forming concentration, suggesting a mechanism where TUDCA directly sequesters drugs. Indeed, in several assays, TUDCA treated cells closely resembled cells treated with lower doses of Tm. In addition, we found TUDCA can inhibit dyes from labeling intracellular compartments. Thus, our study challenges the model of TUDCA as a chemical chaperone and suggests that TUDCA decreases drug bioavailability, allowing cells to adapt to ER stress.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mbcE24040147"},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cryo-electron tomography of eel sperm flagella reveals a molecular "minimum system" for motile cilia.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-11 DOI: 10.1091/mbc.E24-08-0351

Jason R Schrad, Gang Fu, Whitney E Hable, Alexandra M Tayar, Kenneth Oliveira, Daniela Nicastro

{"title":"Cryo-electron tomography of eel sperm flagella reveals a molecular \"minimum system\" for motile cilia.","authors":"Jason R Schrad, Gang Fu, Whitney E Hable, Alexandra M Tayar, Kenneth Oliveira, Daniela Nicastro","doi":"10.1091/mbc.E24-08-0351","DOIUrl":"https://doi.org/10.1091/mbc.E24-08-0351","url":null,"abstract":"Cilia and flagella play a crucial role in the development and function of eukaryotes. The activity of thousands of dyneins is precisely regulated to generate flagellar motility. The complex proteome (600+ proteins) and architecture of the structural core of flagella, the axoneme, have made it challenging to dissect the functions of the different complexes, like the regulatory machinery. Previous reports suggested that the flagellum of American eel sperm lacks many of the canonical axonemal complexes yet is still motile. Here, we use cryo-electron tomography for molecular characterization of this proposed \"minimal\" motile flagellum. We observed different diameters for the eel sperm flagellum: narrow at the base and wider towards the flagellar tip. Subtomogram averaging revealed the 3D-structure of the eel sperm flagellum. As expected, major complexes were missing, e.g., outer dynein arms, radial spokes, and the central-pair-complex, but we found molecular remnants of most complexes. We also identified bend-direction specific patterns in the inter-DMT distance in actively beating eel sperm flagella and we propose a model for the regulation of dynein activity during their motility. Together, our results shed light on the structure and function of the eel sperm flagellum and provide insight into the minimum requirements for ciliary beating. [Media: see text].","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mbcE24080351"},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-04 DOI: 10.1091/mbc.E24-04-0197

Allison Langley, Sarah Abeling-Wang, Erinn Wagner, John Salogiannis

{"title":"Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases.","authors":"Allison Langley, Sarah Abeling-Wang, Erinn Wagner, John Salogiannis","doi":"10.1091/mbc.E24-04-0197","DOIUrl":"10.1091/mbc.E24-04-0197","url":null,"abstract":"Peripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding along stable microtubules via molecular motors or attaching to the plus ends of dynamic microtubules through tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling ER tubules along microtubules. Previous research showed that ER hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do the same. In U2OS cells, we screened Rabs for their ability to cotransport with ER tubules and found that ER hitchhikes on post-Golgi vesicles marked by Rab6 (isoforms a and b). Rab6-ER hitchhiking occurs independently of ER-endolysosome contacts and TAC-mediated ER movement. Depleting Rab6 and the motility of Rab6-vesicles reduces overall ER movement. Conversely, relocating these vesicles to the cell periphery causes peripheral ER accumulation, indicating that Rab6-vesicle motility is crucial for a subset of ER movements. Proximal post-Golgi vesicles marked by TGN46 are involved in Rab6-ER hitchhiking, while late Golgi vesicles (Rabs 8/10/11/13/14) are not essential for ER movement. Our further analysis finds that ER to Golgi vesicles marked by Rab1 are also capable of driving a subset of ER movements. Taken together, our findings suggest that ER hitchhiking on Rab-vesicles is a significant mode of ER movement. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mbcE24040197"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remodeling of cytoskeleton, chromatin and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-12-04 DOI: 10.1091/mbc.E24-09-0430

Trinadha Rao Sornapudi, Luezhen Yuan, Jana Muriel Braunger, Caroline Uhler, G V Shivashankar

{"title":"Remodeling of cytoskeleton, chromatin and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.","authors":"Trinadha Rao Sornapudi, Luezhen Yuan, Jana Muriel Braunger, Caroline Uhler, G V Shivashankar","doi":"10.1091/mbc.E24-09-0430","DOIUrl":"https://doi.org/10.1091/mbc.E24-09-0430","url":null,"abstract":"Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been explored. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. Here, we studied the cytoskeletal, genome-wide chromatin and transcriptional changes in young, aged and mechanically rejuvenated fibroblasts using immunofluorescence, RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had partially reset their transcription to a younger cell state, showed a local reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased acto-myosin contractility like younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Overall, our results give an overview of how changes in the cytoskeleton, chromatin, and gene activity are connected to aging and rejuvenation.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"mbcE24090430"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner.

IF 3.1 3区生物学

Molecular Biology of the Cell Pub 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 (BMDMs) 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 osteoclast differentiation. This is partly attributed to MRTF's 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 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":"mbcE24060285"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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":"","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":"","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":"","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":"","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":"","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":"","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