Molecular Biology of the Cell最新文献_第9页

Dimerization activates the Inversin complex in C. elegans. 二聚化激活了秀丽隐杆线虫中的 Inversin 复合物。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1091/mbc.E24-05-0218

Erika Beyrent, Derek T Wei, Gwendolyn M Beacham, Sangwoo Park, Jian Zheng, Matthew J Paszek, Gunther Hollopeter

{"title":"Dimerization activates the Inversin complex in C. elegans.","authors":"Erika Beyrent, Derek T Wei, Gwendolyn M Beacham, Sangwoo Park, Jian Zheng, Matthew J Paszek, Gunther Hollopeter","doi":"10.1091/mbc.E24-05-0218","DOIUrl":"10.1091/mbc.E24-05-0218","url":null,"abstract":"Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static \"Inversin complex\" or one that adopts multiple bioactive forms. Through the characterization of hyperactive alleles in C. elegans, we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologues of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL-2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states - an active dimer and an inactive monomer - gates the output of the Inversin complex.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar127"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902364","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

Calcineurin promotes adaptation to chronic stress through two distinct mechanisms. 钙调素通过两种不同的机制促进对慢性压力的适应。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1091/mbc.E24-03-0122

Mackenzie J Flynn, Nicholas W Harper, Rui Li, Lihua Julie Zhu, Michael J Lee, Jennifer A Benanti

{"title":"Calcineurin promotes adaptation to chronic stress through two distinct mechanisms.","authors":"Mackenzie J Flynn, Nicholas W Harper, Rui Li, Lihua Julie Zhu, Michael J Lee, Jennifer A Benanti","doi":"10.1091/mbc.E24-03-0122","DOIUrl":"10.1091/mbc.E24-03-0122","url":null,"abstract":"Adaptation to environmental stress requires coordination between stress-defense programs and cell cycle progression. The immediate response to many stressors has been well characterized, but how cells survive in challenging environments long term is unknown. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in adaptation to chronic CaCl2 stress in Saccharomyces cerevisiae. We find that prolonged exposure to CaCl2 impairs mitochondrial function and demonstrate that cells respond to this stressor using two CN-dependent mechanisms-one that requires the downstream transcription factor Crz1 and another that is Crz1 independent. Our data indicate that CN maintains cellular fitness by promoting cell cycle progression and preventing CaCl2-induced cell death. When Crz1 is present, transient CN activation suppresses cell death and promotes adaptation despite high levels of mitochondrial loss. However, in the absence of Crz1, prolonged activation of CN prevents mitochondrial loss and further cell death by upregulating glutathione biosynthesis genes thereby mitigating damage from reactive oxygen species. These findings illustrate how cells maintain long-term fitness during chronic stress and suggest that CN promotes adaptation in challenging environments by multiple mechanisms.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar123"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860283","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 single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers. 一种来自多极端耐受性酵母的单一septin重现了septin异质配体的许多典型功能。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-28 DOI: 10.1091/mbc.E24-05-0227

Grace E Hamilton, Katherine N Wadkovsky, Amy S Gladfelter

{"title":"A single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers.","authors":"Grace E Hamilton, Katherine N Wadkovsky, Amy S Gladfelter","doi":"10.1091/mbc.E24-05-0227","DOIUrl":"10.1091/mbc.E24-05-0227","url":null,"abstract":"Morphological complexity and plasticity are hallmarks of polyextremotolerant fungi. Septins are conserved cytoskeletal proteins and key contributors to cell polarity and morphogenesis. They sense membrane curvature, coordinate cell division, and influence diffusion at the plasma membrane. Four septin homologues are conserved from yeasts to humans, the systems in which septins have been most studied. But there is also a fifth family of opisthokont septins that remain biochemically mysterious. Members of this family, Group 5 septins, appear in the genomes of filamentous fungi, but are understudied due to their absence from ascomycete yeasts. Knufia petricola is an emerging model polyextremotolerant black fungus that can also serve as a model system for Group 5 septins. We have recombinantly expressed and biochemically characterized KpAspE, a Group 5 septin from K. petricola. This septin--by itself in vitro--recapitulates many functions of canonical septin hetero-octamers. KpAspE is an active GTPase that forms diverse homo-oligomers, binds shallow membrane curvatures, and interacts with the terminal subunit of canonical septin hetero-octamers. These findings raise the possibility that Group 5 septins govern the higher-order structures formed by canonical septins, which in K. petricola cells form extended filaments, and provide insight into how septin hetero-oligomers evolved from ancient homomers.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar132"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086178","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

Shared and redundant proteins coordinate signal cross-talk between MAPK pathways in yeast. 共享和冗余蛋白协调酵母中 MAPK 通路之间的信号交叉。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1091/mbc.E24-06-0270

Shu Zhang, Hao Wang, Emily L Sipko, Shuang Li, Timothy A Daugird, Wesley R Legant, Henrik G Dohlman

{"title":"Shared and redundant proteins coordinate signal cross-talk between MAPK pathways in yeast.","authors":"Shu Zhang, Hao Wang, Emily L Sipko, Shuang Li, Timothy A Daugird, Wesley R Legant, Henrik G Dohlman","doi":"10.1091/mbc.E24-06-0270","DOIUrl":"10.1091/mbc.E24-06-0270","url":null,"abstract":"All cells must detect, interpret, and adapt to multiple and concurrent stimuli. While signaling pathways are highly specialized, different pathways often share components or have components with overlapping functions. In the yeast Saccharomyces cerevisiae, the high osmolarity glycerol (HOG) pathway has two seemingly redundant branches, mediated by Sln1 and Sho1. Both branches are activated by osmotic pressure, leading to phosphorylation of the MAPKs Hog1 and Kss1. The mating pathway is activated by pheromone, leading to phosphorylation of the MAPKs Fus3 and Kss1. Given that Kss1 is shared by the two pathways, we investigated its role in signal coordination. We activated both pathways with a combination of salt and pheromone, in cells lacking the shared MAPK and in cells lacking either of the redundant branches of the HOG pathway. By systematically evaluating MAPK activation, translocation, and transcription programs, we determined that Sho1 mediates cross talk between the HOG and mating pathways and does so through Kss1. Further, we show that Kss1 initiates a transcriptional program that is distinct from that induced by Hog1 and Fus3. Our findings reveal how redundant and shared components coordinate concurrent signals and thereby adapt to sudden environmental changes.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar126"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860285","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

Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation. 亚砷酸钠通过促进 PICK1 BAR 结构域同源二聚体的形成来诱导凝集体的形成。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1091/mbc.E24-05-0201

John Ho Chun Lai, Marianthi Tsogka, Jun Xia

引用次数: 0

The Role of Nde1 phosphorylation in interkinetic nuclear migration and neural migration during cortical development. Nde1 磷酸化在皮层发育过程中的动核间迁移和神经迁移中的作用

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1091/mbc.E24-05-0217

David J Doobin, Paige Helmer, Aurelie Carabalona, Chiara Bertipaglia, Richard B Vallee

{"title":"The Role of Nde1 phosphorylation in interkinetic nuclear migration and neural migration during cortical development.","authors":"David J Doobin, Paige Helmer, Aurelie Carabalona, Chiara Bertipaglia, Richard B Vallee","doi":"10.1091/mbc.E24-05-0217","DOIUrl":"10.1091/mbc.E24-05-0217","url":null,"abstract":"Nde1 is a cytoplasmic dynein regulatory protein with important roles in vertebrate brain development. One noteworthy function is in the nuclear oscillatory behavior in neural progenitor cells, the control and mechanism of which remain poorly understood. Nde1 contains multiple phosphorylation sites for the cell cycle-dependent protein kinase CDK1, though the function of these sites is not well understood. To test their role in brain development, we expressed phosphorylation-state mutant forms of Nde1 in embryonic rat brains using in utero electroporation. We find that Nde1 T215 and T243 phosphomutants block apical interkinetic nuclear migration (INM) and, consequently, mitosis in radial glial progenitor cells. Another Nde1 phosphomutant at T246 also interfered with mitotic entry without affecting INM, suggesting a more direct role for Nde1 T246 in mitotic regulation. We also found that the Nde1 S214F mutation, which is associated with schizophrenia, inhibits Cdk5 phosphorylation at an adjacent residue which causes alterations in neuronal lamination. These results together identify important new roles for Nde1 phosphorylation in neocortical development and disease, and represent the first evidence for Nde1 phosphorylation roles in INM and neuronal lamination.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar129"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017996","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

mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration. mDia2是MRTF-A依赖性调控乳腺癌细胞迁移的重要介质。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-08-28 DOI: 10.1091/mbc.E24-01-0008

Ian Eder, Virginia Yu, Jacob Antonello, Fangyuan Chen, David Gau, Pooja Chawla, Marion Joy, Peter C Lucas, David Boone, Adrian V Lee, Partha Roy

{"title":"mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration.","authors":"Ian Eder, Virginia Yu, Jacob Antonello, Fangyuan Chen, David Gau, Pooja Chawla, Marion Joy, Peter C Lucas, David Boone, Adrian V Lee, Partha Roy","doi":"10.1091/mbc.E24-01-0008","DOIUrl":"10.1091/mbc.E24-01-0008","url":null,"abstract":"Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type versus functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF's interaction is critical for MRTF-A-induced promotion of both two-dimensional and three-dimensional cell migration, while the SAP-domain function is important selectively for three-dimensional cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF's interaction with MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases versus primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human BC, justifying future development of specific small molecule inhibitors of the MRTF-SRF transcriptional complex as potential therapeutic agents in BC.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar133"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086179","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

Viral imitation is the sincerest form of epigenetic flattery. 病毒式模仿是表观遗传学最真诚的奉承。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-10-01 DOI: 10.1091/mbc.E23-04-0147

Julian R Smith, Angela A Arellano, Daphne C Avgousti

引用次数: 0

Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites. 生长因子受体系统在凝集素包被位点的空间和信号重叠。

IF 3.3 3区生物学

Molecular Biology of the Cell Pub Date : 2024-09-18 DOI: 10.1091/mbc.e24-05-0226

Marco A Alfonzo-Méndez,Marie-Paule Strub,Justin W Taraska

{"title":"Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.","authors":"Marco A Alfonzo-Méndez,Marie-Paule Strub,Justin W Taraska","doi":"10.1091/mbc.e24-05-0226","DOIUrl":"https://doi.org/10.1091/mbc.e24-05-0226","url":null,"abstract":"Cellular communication is regulated at the plasma membrane by the interactions of receptor, adhesion, signaling, and endocytic proteins. Yet, the composition and control of these complexes in response to external cues remain unclear. We use high-resolution and high-throughput fluorescence imaging to map the localization of growth factor receptors and related proteins at single clathrin-coated structures in human squamous HSC3 cells. We find distinct protein signatures between control cells and cells stimulated with growth factors. Clathrin sites at the plasma membrane are preloaded with some receptors but not others. Stimulation with epidermal growth factor induces capture and concentration of epidermal growth factor-, fibroblast growth factor-, and low-density lipoprotein-receptors (EGFR, FGFR1, and LDLR). Regulatory proteins including ubiquitin ligase Cbl, the scaffold Grb2, and the mechanoenzyme dynamin2 are also recruited. Disrupting FGFR or EGFR activity with drugs prevents the recruitment of both EGFR and FGFR1. EGF was able to activate FGFR1 phosphorylation. Our data reveals novel co-clustering and activation of receptors and regulatory factors at clathrin-coated sites in response to stimulation by a single growth factor, EGF or FGF. This behavior integrates growth factor signaling and allows for complex responses to extracellular cues and drugs at the plasma membrane of human cells.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"40 1","pages":"mbcE24050226"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265312","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

RAD51 regulates eukaryotic chromatin motions in the absence of DNA damage. RAD51 在没有 DNA 损伤的情况下调节真核染色质的运动。

IF 3.3 3区生物学

Molecular Biology of the Cell Pub Date : 2024-09-18 DOI: 10.1091/mbc.e24-04-0188

Amine Maarouf,Fadil Iqbal,Sarvath Sanaullah,Maëlle Locatelli,Andrew T Atanasiu,Daniel Kolbin,Chloé Hommais,Joëlle Mühlemann,Keith Bonin,Kerry Bloom,Jing Liu,Pierre-Alexandre Vidi

{"title":"RAD51 regulates eukaryotic chromatin motions in the absence of DNA damage.","authors":"Amine Maarouf,Fadil Iqbal,Sarvath Sanaullah,Maëlle Locatelli,Andrew T Atanasiu,Daniel Kolbin,Chloé Hommais,Joëlle Mühlemann,Keith Bonin,Kerry Bloom,Jing Liu,Pierre-Alexandre Vidi","doi":"10.1091/mbc.e24-04-0188","DOIUrl":"https://doi.org/10.1091/mbc.e24-04-0188","url":null,"abstract":"In yeasts and higher eukaryotes, chromatin motions may be tuned to genomic functions, with transcriptional activation and the DNA damage response both leading to profound changes in chromatin dynamics. The RAD51 recombinase is a key mediator of chromatin mobility following DNA damage. As functions of RAD51 beyond DNA repair are being discovered, we asked if RAD51 modulates chromatin dynamics in the absence of DNA damage and found that inhibition or depletion of RAD51 alters chromatin motions in undamaged cells. Inhibition of RAD51 increased nucleosome clustering. Predictions from polymer models are that chromatin clusters reduce chain mobility and, indeed, we measured reduced motion of individual chromatin loci in cells treated with a RAD51 inhibitor. This effect was conserved in mammalian cells, yeasts, and plant cells. In contrast, RAD51 depletion or inhibition increased global chromatin motions at the microscale. The results uncover a role for RAD51 in regulating local and global chromatin dynamics independently from DNA damage and highlight the importance of considering different physical scales when studying chromatin dynamics.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"22 1","pages":"mbcE24040188"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269415","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