Molecular Biology of the Cell最新文献_第9页

An invariant C-terminal tryptophan in McdB mediates its interaction and positioning function with carboxysomes. McdB 中一个不变的 C 端色氨酸介导了它与羧基体的相互作用和定位功能。

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.E23-11-0443

Joseph L Basalla, Maria Ghalmi, Y Hoang, Rachel E Dow, Anthony G Vecchiarelli

{"title":"An invariant C-terminal tryptophan in McdB mediates its interaction and positioning function with carboxysomes.","authors":"Joseph L Basalla, Maria Ghalmi, Y Hoang, Rachel E Dow, Anthony G Vecchiarelli","doi":"10.1091/mbc.E23-11-0443","DOIUrl":"10.1091/mbc.E23-11-0443","url":null,"abstract":"Bacterial microcompartments (BMCs) are widespread, protein-based organelles that regulate metabolism. The model for studying BMCs is the carboxysome, which facilitates carbon fixation in several autotrophic bacteria. Carboxysomes can be distinguished as type α or β, which are structurally and phyletically distinct. We recently characterized the maintenance of carboxysome distribution (Mcd) systems responsible for spatially regulating α- and β-carboxysomes, consisting of the proteins McdA and McdB. McdA is an ATPase that drives carboxysome positioning, and McdB is the adaptor protein that directly interacts with carboxysomes to provide cargo specificity. The molecular features of McdB proteins that specify their interactions with carboxysomes, and whether these are similar between α- and β-carboxysomes, remain unknown. Here, we identify C-terminal motifs containing an invariant tryptophan necessary for α- and β-McdBs to associate with α- and β-carboxysomes, respectively. Substituting this tryptophan with other aromatic residues reveals corresponding gradients in the efficiency of carboxysome colocalization and positioning by McdB in vivo. Intriguingly, these gradients also correlate with the ability of McdB to form condensates in vitro. The results reveal a shared mechanism underlying McdB adaptor protein binding to carboxysomes, and potentially other BMCs. Our findings also implicate condensate formation as playing a key role in this association.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar107"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458065","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

Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids. 简单非整倍体可逃避 p53 的监控，并促进人体肠道器官组织中不依赖于生态位因子的生长。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-04-0166

Blake A Johnson, Albert Z Liu, Tianhao Bi, Yi Dong, Taibo Li, Dingjingyu Zhou, Akshay Narkar, Yufei Wu, Sean X Sun, Tatianna C Larman, Jin Zhu, Rong Li

{"title":"Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids.","authors":"Blake A Johnson, Albert Z Liu, Tianhao Bi, Yi Dong, Taibo Li, Dingjingyu Zhou, Akshay Narkar, Yufei Wu, Sean X Sun, Tatianna C Larman, Jin Zhu, Rong Li","doi":"10.1091/mbc.E24-04-0166","DOIUrl":"10.1091/mbc.E24-04-0166","url":null,"abstract":"Aneuploidy is nearly ubiquitous in tumor genomes, but the role of aneuploidy in the early stages of cancer evolution remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigated how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Previous work implicated p53 activation as a downstream response to aneuploidy induction. We found that simple aneuploidy, characterized by 1-3 gained or lost chromosomes, resulted in little or modest p53 activation and cell cycle arrest when compared with more complex aneuploid cells. Single-cell RNA sequencing analysis revealed that the degree of p53 activation was strongly correlated with karyotype complexity. Single-cell tracking showed that cells could continue to divide despite the observation of one to a few lagging chromosomes. Unexpectedly, colonoids with simple aneuploidy exhibited impaired differentiation after niche factor withdrawal. These findings demonstrate that simple aneuploid cells can escape p53 surveillance and may contribute to niche factor-independent growth of cancer-initiating colon stem cells.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br15"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580243","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

LRRC56 is an IFT cargo required for assembly of the distal dynein docking complex in Trypanosoma brucei. LRRC56 是布氏锥虫远端动力蛋白对接复合物组装所需的 IFT 货物。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-12 DOI: 10.1091/mbc.E23-11-0425

Serge Bonnefoy, Aline Araujo Alves, Eloïse Bertiaux, Philippe Bastin

{"title":"LRRC56 is an IFT cargo required for assembly of the distal dynein docking complex in Trypanosoma brucei.","authors":"Serge Bonnefoy, Aline Araujo Alves, Eloïse Bertiaux, Philippe Bastin","doi":"10.1091/mbc.E23-11-0425","DOIUrl":"10.1091/mbc.E23-11-0425","url":null,"abstract":"Outer dynein arms (ODAs) are responsible for ciliary beating in eukaryotes. They are assembled in the cytoplasm and shipped by intraflagellar transport (IFT) before attachment to microtubule doublets via the docking complex. The LRRC56 protein has been proposed to contribute to ODAs maturation. Mutations or deletion of the LRRC56 gene lead to reduced ciliary motility in all species investigated so far, but with variable impact on dynein arm presence. Here, we investigated the role of LRRC56 in the protist Trypanosoma brucei, where its absence results in distal loss of ODAs, mostly in growing flagella. We show that LRRC56 is a transient cargo of IFT trains during flagellum construction and surprisingly, is required for efficient attachment of a subset of docking complex proteins present in the distal portion of the organelle. This relation is interdependent since the knockdown of the distal docking complex prevents LRRC56's association with the flagellum. Intriguingly, lrrc56-/- cells display shorter flagella whose maturation is delayed. Inhibition of cell division compensates for the distal ODAs absence thanks to the redistribution of the proximal docking complex, restoring ODAs attachment but not the flagellum length phenotype. This work reveals an unexpected connection between LRRC56 and the docking complex.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar106"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306299","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 core spindle pole body scaffold Ppc89 links the pericentrin orthologue Pcp1 to the fission yeast spindle pole body via an evolutionarily conserved interface. 核心纺锤极体支架Ppc89通过一个进化保守的界面将包心蛋白直向同源物Pcp1与裂殖酵母纺锤极体连接起来。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-05-0220

Jun-Song Chen, Maya G Igarashi, Liping Ren, Sarah M Hanna, Lesley A Turner, Nathan A McDonald, Janel R Beckley, Alaina H Willet, Kathleen L Gould

{"title":"The core spindle pole body scaffold Ppc89 links the pericentrin orthologue Pcp1 to the fission yeast spindle pole body via an evolutionarily conserved interface.","authors":"Jun-Song Chen, Maya G Igarashi, Liping Ren, Sarah M Hanna, Lesley A Turner, Nathan A McDonald, Janel R Beckley, Alaina H Willet, Kathleen L Gould","doi":"10.1091/mbc.E24-05-0220","DOIUrl":"10.1091/mbc.E24-05-0220","url":null,"abstract":"Centrosomes and spindle pole bodies (SPBs) are important for mitotic spindle formation and serve as cellular signaling platforms. Although centrosomes and SPBs differ in morphology, many mechanistic insights into centrosome function have been gleaned from SPB studies. In the fission yeast Schizosaccharomyces pombe, the α-helical protein Ppc89, identified based on its interaction with the septation initiation network scaffold Sid4, comprises the SPB core. High-resolution imaging has suggested that SPB proteins assemble on the Ppc89 core during SPB duplication, but such interactions are undefined. Here, we define a connection between Ppc89 and the essential pericentrin Pcp1. Specifically, we found that a predicted third helix within Ppc89 binds the Pcp1 pericentrin-AKAP450 centrosomal targeting (PACT) domain complexed with calmodulin. Ppc89 helix 3 contains similarity to present in the N-terminus of Cep57 (PINC) motifs found in the centrosomal proteins fly SAS-6 and human Cep57 and also to the S. cerevisiae SPB protein Spc42. These motifs bind pericentrin-calmodulin complexes and AlphaFold2 models suggest a homologous complex assembles in all four organisms. Mutational analysis of the S. pombe complex supports the importance of Ppc89-Pcp1 binding interface in vivo. Our studies provide insight into the core architecture of the S. pombe SPB and suggest an evolutionarily conserved mechanism of scaffolding pericentrin-calmodulin complexes for mitotic spindle formation.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar112"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580245","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

TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport. TFG 可调节 COPII 内膜的募集，从而促进分泌蛋白的前向运输。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-06-0282

William Kasberg, Peter Luong, Kayla Minushkin, Iryna Pustova, Kevin A Swift, Meixian Zhao, Anjon Audhya

{"title":"TFG regulates inner COPII coat recruitment to facilitate anterograde secretory protein transport.","authors":"William Kasberg, Peter Luong, Kayla Minushkin, Iryna Pustova, Kevin A Swift, Meixian Zhao, Anjon Audhya","doi":"10.1091/mbc.E24-06-0282","DOIUrl":"10.1091/mbc.E24-06-0282","url":null,"abstract":"Coat protein complex II (COPII) governs the initial steps of biosynthetic secretory protein transport from the endoplasmic reticulum (ER), facilitating the movement of a wide variety of cargoes. Here, we demonstrate that Trk-fused gene (TFG) regulates the rate at which inner COPII coat proteins are concentrated at ER subdomains. Specifically, in cells lacking TFG, the GTPase-activating protein (GAP) Sec23 accumulates more rapidly at budding sites on the ER as compared with control cells, potentially altering the normal timing of GTP hydrolysis on Sar1. Under these conditions, anterograde trafficking of several secretory cargoes is delayed, irrespective of their predicted size. We propose that TFG controls the local, freely available pool of Sec23 during COPII coat formation and limits its capacity to prematurely destabilize COPII complexes on the ER. This function of TFG enables it to act akin to a rheostat, promoting the ordered recruitment of Sec23, which is critical for efficient secretory cargo export.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar113"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580244","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

Image-based discrimination of the early stages of mesenchymal stem cell differentiation. 基于图像辨别间充质干细胞分化的早期阶段。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-05 DOI: 10.1091/mbc.E24-02-0095

Justin Hoffman, Shiyuan Zheng, Huaiying Zhang, Robert F Murphy, Kris Noel Dahl

{"title":"Image-based discrimination of the early stages of mesenchymal stem cell differentiation.","authors":"Justin Hoffman, Shiyuan Zheng, Huaiying Zhang, Robert F Murphy, Kris Noel Dahl","doi":"10.1091/mbc.E24-02-0095","DOIUrl":"10.1091/mbc.E24-02-0095","url":null,"abstract":"Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells, which can be used in cellular and tissue therapeutics. MSCs cell number can be expanded in vitro, but premature differentiation results in reduced cell number and compromised therapeutic efficacies. Current techniques fail to discriminate the \"stem-like\" population from early stages (12 h) of differentiated MSC population. Here, we imaged nuclear structure and actin architecture using immunofluorescence and used deep learning-based computer vision technology to discriminate the early stages (6-12 h) of MSC differentiation. Convolutional neural network models trained by nucleus and actin images have high accuracy in reporting MSC differentiation; nuclear images alone can identify early stages of differentiation. Concurrently, we show that chromatin fluidity and heterochromatin levels or localization change during early MSC differentiation. This study quantifies changes in cell architecture during early MSC differentiation and describes a novel image-based diagnostic tool that could be widely used in MSC culture, expansion and utilization.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar103"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262024","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

Maximizing Access to Cell Biology for PEERS: Retracting the term minority in favor of a more inclusive lexicon. 最大限度地为 PEERS 提供细胞生物学知识：收回 "少数群体 "一词，使用更具包容性的词汇。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 DOI: 10.1091/mbc.E24-04-0156

Fernando Vonhoff, Dana-Lynn Ko'omoa-Lange, Jamaine S Davis, Christina M Termini, Michelle M Martínez-Montemayor

{"title":"Maximizing Access to Cell Biology for PEERS: Retracting the term minority in favor of a more inclusive lexicon.","authors":"Fernando Vonhoff, Dana-Lynn Ko'omoa-Lange, Jamaine S Davis, Christina M Termini, Michelle M Martínez-Montemayor","doi":"10.1091/mbc.E24-04-0156","DOIUrl":"10.1091/mbc.E24-04-0156","url":null,"abstract":"The word minority, when used incorrectly, is a condescending term that segregates, inaccurately represents groups as being smaller or less important, and fuels microaggressions. Scientific societies and other institutions have normalized using the word minority, or the \"M word,\" to refer to members of underrepresented groups in Science, Technology, Engineering, and Mathematics (STEM). The message put forth using the term minority often directly conflicts with the inclusive agenda these societies seek to enact. More inclusive acronyms such as PEER (Persons Excluded because of their Ethnicity or Race) have been created to more accurately reflect the active process of exclusion by institutions. Here, we detail the rationale behind the decision to eradicate the word minority from the name of a prominent committee within the American Society for Cell Biology (ASCB). The ASCB Minority Affairs Committee changed its name to the Maximizing Access to Cell Biology for PEERS Committee. Herein, we emphasize the basis for the name change and highlight the contradictions intrinsic to the word minority in this context. We highlight why swift action is required for this rewording within the context of a committee dedicated to supporting the inclusion of PEERs in the scientific community.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"35 8","pages":"vo1"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590772","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

Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro. 特发性肺纤维化患者肺基质衍生水凝胶诱导体外肺成纤维细胞的促炎状态

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E23-11-0428

Jorge G Fernandez Davila, Amit K Singh, Durwood W Moore, Joseph Kim, Jawad A Khan, Merte Lemma, Christopher S King, Steven D Nathan, Luis R Rodriguez, Geraldine M Grant, Jeffrey L Moran

{"title":"Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro.","authors":"Jorge G Fernandez Davila, Amit K Singh, Durwood W Moore, Joseph Kim, Jawad A Khan, Merte Lemma, Christopher S King, Steven D Nathan, Luis R Rodriguez, Geraldine M Grant, Jeffrey L Moran","doi":"10.1091/mbc.E23-11-0428","DOIUrl":"10.1091/mbc.E23-11-0428","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from patients with IPF, we generate three-dimensional hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF extracellular matrix hydrogels, IPF fibroblasts display differential contractility compared with their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared with fibroblasts seeded two-dimensionally on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell cross-talk as a possible novel therapeutic avenue.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar114"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580242","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

Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners. 揭示肺癌上皮细胞可塑性调控：探索 Tks4 支架蛋白伙伴间的相互关系。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-03-0103

Loretta László, Anita Kurilla, Álmos Tilajka, Rita Pancsa, Tamás Takács, Julianna Novák, László Buday, Virag Vas

{"title":"Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners.","authors":"Loretta László, Anita Kurilla, Álmos Tilajka, Rita Pancsa, Tamás Takács, Julianna Novák, László Buday, Virag Vas","doi":"10.1091/mbc.E24-03-0103","DOIUrl":"10.1091/mbc.E24-03-0103","url":null,"abstract":"The epithelial-to-mesenchymal transition (EMT) represents a hallmark event in the evolution of lung cancer. This work aims to study a recently described EMT-regulating protein, Tks4, and to explore its potential as a prognostic biomarker in non-small cell lung cancer. In this study, we used CRISPR/Cas9 method to knockout (KO) Tks4 to study its functional roles in invadopodia formation, migration, and regulation of EMT marker expressions and we identified Tks4-interacting proteins. Tks4-KO A549 cells exhibited an EMT-like phenotype characterized by elongated morphology and increased expression of EMT markers. Furthermore, analyses of a large-scale lung cancer database and a patient-derived tissue array data revealed that the Tks4 mRNA level was decreased in more aggressive lung cancer stages. To understand the regulatory role of Tks4 in lung cancer, we performed a Tks4-interactome analysis via Tks4 immunoprecipitation-mass spectrometry on five different cell lines and identified CAPZA1 as a novel Tks4 partner protein. Thus, we propose that the absence of Tks4 leads to disruption of a connectome of multiple proteins and that the resulting undocking and likely mislocalization of signaling molecules impairs actin cytoskeleton rearrangement and activates EMT-like cell fate switches, both of which likely influence disease severity.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar111"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580247","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 RNA-binding protein Nab2 regulates levels of the RhoGEF Trio to govern axon and dendrite morphology. RNA 结合蛋白 Nab2 可调节 RhoGEF Trio 的水平，从而控制轴突和树突的形态。

IF 3.1 3区生物学

Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-07-10 DOI: 10.1091/mbc.E24-04-0150

Carly L Lancaster, Pranav S Yalamanchili, Jordan N Goldy, Sara W Leung, Anita H Corbett, Kenneth H Moberg

{"title":"The RNA-binding protein Nab2 regulates levels of the RhoGEF Trio to govern axon and dendrite morphology.","authors":"Carly L Lancaster, Pranav S Yalamanchili, Jordan N Goldy, Sara W Leung, Anita H Corbett, Kenneth H Moberg","doi":"10.1091/mbc.E24-04-0150","DOIUrl":"10.1091/mbc.E24-04-0150","url":null,"abstract":"The Drosophila RNA-binding protein (RBP) Nab2 acts in neurons to regulate neurodevelopment and is orthologous to the human intellectual disability-linked RBP, ZC3H14. Nab2 governs axon projection in mushroom body neurons and limits dendritic arborization of class IV sensory neurons in part by regulating splicing events in ∼150 mRNAs. Analysis of the Sex-lethal (Sxl) mRNA revealed that Nab2 promotes an exon-skipping event and regulates m6A methylation on Sxl pre-mRNA by the Mettl3 methyltransferase. Mettl3 heterozygosity broadly rescues Nab2null phenotypes implying that Nab2 acts through similar mechanisms on other RNAs, including unidentified targets involved in neurodevelopment. Here, we show that Nab2 and Mettl3 regulate the removal of a 5'UTR (untranslated region) intron in the trio pre-mRNA. Trio utilizes two GEF domains to balance Rac and RhoGTPase activity. Intriguingly, an isoform of Trio containing only the RhoGEF domain, GEF2, is depleted in Nab2null nervous tissue. Expression of Trio-GEF2 rescues projection defects in Nab2null axons and dendrites, while the GEF1 Rac1-regulatory domain exacerbates these defects, suggesting Nab2-mediated regulation Trio-GEF activities. Collectively, these data indicate that Nab2-regulated processing of trio is critical for balancing Trio-GEF1 and -GEF2 activity and show that Nab2, Mettl3, and Trio function in a common pathway that shapes axon and dendrite morphology.","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar109"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580246","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