Molecular Biology of the Cell最新文献_第7页

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

FHOD-1 and profilin protect sarcomeres against contraction-induced deformation in C. elegans. FHOD-1 和 profilin 可保护秀丽隐杆线虫的肌节免受收缩引起的变形。

IF 3.3 3区生物学

Molecular Biology of the Cell Pub Date : 2024-09-11 DOI: 10.1091/mbc.e24-04-0145

Michael J Kimmich,Sumana Sundaramurthy,Meaghan A Geary,Leila Lesanpezeshki,Curtis V Yingling,Siva A Vanapalli,Ryan S Littlefield,David Pruyne

{"title":"FHOD-1 and profilin protect sarcomeres against contraction-induced deformation in C. elegans.","authors":"Michael J Kimmich,Sumana Sundaramurthy,Meaghan A Geary,Leila Lesanpezeshki,Curtis V Yingling,Siva A Vanapalli,Ryan S Littlefield,David Pruyne","doi":"10.1091/mbc.e24-04-0145","DOIUrl":"https://doi.org/10.1091/mbc.e24-04-0145","url":null,"abstract":"Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from Caenorhabditis elegans results in thin body wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that mutations predicted to specifically disrupt actin polymerization by FHOD-1 similarly disrupt muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and with profilins PFN-2 and PFN-3 to promote body wall muscle growth. We further demonstrate that dense bodies in worms lacking FHOD-1 or PFN-2/PFN-3 are less stable than in wild type animals, having a higher proportion of dynamic protein, and becoming distorted by prolonged muscle contraction. We also observe accumulation of actin and actin depolymerization factor/cofilin homolog UNC-60B in body wall muscle of these mutants. Such accumulations may indicate targeted disassembly of thin filaments dislodged from unstable dense bodies, possibly accounting for the abnormally slow growth and reduced body wall muscle strength in fhod-1 mutants. Overall, these results implicate FHOD protein-mediated actin assembly in forming stable sarcomere Z-lines, and identify profilin as a new contributor to FHOD activity in striated muscle development.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"5 1","pages":"mbcE24040145"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184289","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

The prolyl isomerase FKBP11 is a secretory translocon accessory factor. 脯氨酰异构酶 FKBP11 是一种分泌性转座子附属因子。

IF 3.3 3区生物学

Molecular Biology of the Cell Pub Date : 2024-09-11 DOI: 10.1091/mbc.e24-07-0305

Amanda DiGuilio,Ben Cheng,Frank Zhong,Roshan Jha,Yu Wan,Andrei Anghel,Hong Hu,Evgenia Shishkova,Zhe Ji,Joshua J Coon,Robert J Keenan

{"title":"The prolyl isomerase FKBP11 is a secretory translocon accessory factor.","authors":"Amanda DiGuilio,Ben Cheng,Frank Zhong,Roshan Jha,Yu Wan,Andrei Anghel,Hong Hu,Evgenia Shishkova,Zhe Ji,Joshua J Coon,Robert J Keenan","doi":"10.1091/mbc.e24-07-0305","DOIUrl":"https://doi.org/10.1091/mbc.e24-07-0305","url":null,"abstract":"Eukaryotic cells encode thousands of secretory and membrane proteins, many of which are cotranslationally translocated into or across the endoplasmic reticulum (ER). Nascent polypeptides entering the ER encounter a network of molecular chaperones and enzymes that facilitate their folding. A rate-limiting step for some proteins is the trans-to-cis isomerization of the peptide bond between proline and the residue preceding it. The human ER contains six prolyl isomerases, but the function, organization and substrate range of these proteins is not clear. Here we show that the metazoan-specific, prolyl isomerase FKBP11 binds to ribosome-translocon complexes (RTCs) in the ER membrane, dependent on its single transmembrane domain (TMD) and a conserved, positively charged region at its cytosolic C-terminus. High throughput mRNA sequencing shows selective engagement with ribosomes synthesizing secretory and membrane proteins with long translocated segments, and functional analysis shows reduced stability of two such proteins, EpCAM and PTTG1IP, in cells depleted of FKBP11. We propose that FKBP11 is a translocon accessory factor that acts on a broad range of soluble secretory and transmembrane proteins during their synthesis at the ER.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"10 1","pages":"mbcE24070305"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184291","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

The GTP-tubulin cap is not the determinant of microtubule end stability in cells. GTP-微管蛋白帽并非细胞中微管末端稳定性的决定因素。

IF 3.3 3区生物学

Molecular Biology of the Cell Pub Date : 2024-09-11 DOI: 10.1091/mbc.e24-07-0307

Anna Cassidy,Veronica Farmer,Göker Arpağ,Marija Zanic

{"title":"The GTP-tubulin cap is not the determinant of microtubule end stability in cells.","authors":"Anna Cassidy,Veronica Farmer,Göker Arpağ,Marija Zanic","doi":"10.1091/mbc.e24-07-0307","DOIUrl":"https://doi.org/10.1091/mbc.e24-07-0307","url":null,"abstract":"Microtubules are dynamic cytoskeletal polymers essential for cell division, motility, and intracellular transport. Microtubule dynamics are characterized by dynamic instability-the ability of individual microtubules to switch between phases of growth and shrinkage. Dynamic instability can be explained by the GTP-cap model, suggesting that a 'cap' of GTP-tubulin subunits at the growing microtubule end has a stabilizing effect, protecting against microtubule catastrophe-the switch from growth to shrinkage. Although the GTP-cap is thought to protect the growing microtubule end, whether the GTP-cap size affects microtubule stability in cells is not known. Notably, a family of microtubule end-binding proteins, EBs, recognize the nucleotide state of tubulin and display comet-like localization at growing microtubule ends, which can be used as a proxy for the GTP-cap. Here, we employ high spatiotemporal resolution imaging to compare the relationship between EB comet size and microtubule dynamics in interphase LLC-PK1 cells to that measured in vitro. Our data reveal that the GTP-cap size in cells scales with the microtubule growth rate in the same way as in vitro. However, we find that microtubule ends in cells can withstand transition to catastrophe even after the EB comet is lost. Thus, our findings suggest that the presence of the GTP-cap is not the determinant of microtubule end stability in cells.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"58 1","pages":"mbcE24070307"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184292","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