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Changes in DNA methylation contribute to rapid adaptation in bacterial plant pathogen evolution. DNA 甲基化的变化有助于植物细菌病原体进化过程中的快速适应。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-20 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002792
Rekha Gopalan-Nair, Aurore Coissac, Ludovic Legrand, Céline Lopez-Roques, Yann Pécrix, Céline Vandecasteele, Olivier Bouchez, Xavier Barlet, Anne Lanois, Alain Givaudan, Julien Brillard, Stéphane Genin, Alice Guidot

Adaptation is usually explained by beneficial genetic mutations that are transmitted from parents to offspring and become fixed in the adapted population. However, genetic mutation analysis alone is not sufficient to fully explain the adaptive processes, and several studies report the existence of nongenetic (or epigenetic) inheritance that can enable adaptation to new environments. In the present work, we tested the hypothesis of the role of DNA methylation, a form of epigenetic modification, in adaptation of the plant pathogen Ralstonia pseudosolanacearum to the host during experimental evolution. Using SMRT-seq technology, we analyzed the methylomes of 31 experimentally evolved clones obtained after serial passages on 5 different plant species during 300 generations. Comparison with the methylome of the ancestral clone revealed a list of 50 differential methylated sites (DMSs) at the GTWWAC motif. Gene expression analysis of the 39 genes targeted by these DMSs revealed limited correlation between differential methylation and differential expression of the corresponding genes. Only 1 gene showed a correlation, the RSp0338 gene encoding the EpsR regulator protein. The MSRE-qPCR technology, used as an alternative approach for DNA methylation analysis, also found the 2 DMSs upstream RSp0338. Using site-directed mutagenesis, we demonstrated the contribution of these 2 DMSs in host adaptation. As these DMSs appeared very early in the experimental evolution, we hypothesize that such fast epigenetic changes can allow rapid adaptation to the plant stem environment. In addition, we found that the change in DNA methylation upstream RSp0338 remains stable at least for 100 generations outside the host and thus can contribute to long-term adaptation to the host plant. To our knowledge, this is the first study showing a direct link between bacterial epigenetic variation and adaptation to a new environment.

适应通常是通过有益的基因突变来解释的,这种突变从亲代传给子代,并在适应的种群中固定下来。然而,仅靠基因突变分析并不足以完全解释适应过程,一些研究报告称,非遗传(或表观遗传)的存在可使人们适应新环境。在本研究中,我们检验了 DNA 甲基化(一种表观遗传修饰形式)在植物病原体假丝酵母(Ralstonia pseudosolanacearum)实验进化过程中对宿主的适应过程中所起作用的假设。利用 SMRT-seq 技术,我们分析了在 5 种不同植物上连续传代 300 代后获得的 31 个实验进化克隆的甲基组。通过与祖先克隆的甲基组比较,我们发现在 GTWWAC 主题上有 50 个不同的甲基化位点(DMS)。对这些 DMSs 所针对的 39 个基因进行的基因表达分析表明,甲基化差异与相应基因的差异表达之间的相关性有限。只有一个基因显示出相关性,即编码 EpsR 调节蛋白的 RSp0338 基因。作为 DNA 甲基化分析的另一种方法,MSRE-qPCR 技术也发现了 RSp0338 上游的 2 个 DMS。通过定点突变,我们证明了这 2 个 DMS 在宿主适应中的作用。由于这些 DMSs 在实验进化过程中出现得非常早,我们推测这种快速的表观遗传变化可以让植物茎干环境快速适应。此外,我们还发现,RSp0338上游DNA甲基化的变化在宿主外至少100代保持稳定,因此有助于对宿主植物的长期适应。据我们所知,这是第一项显示细菌表观遗传变异与适应新环境之间直接联系的研究。
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引用次数: 0
Identification of a highly efficient chloroplast-targeting peptide for plastid engineering. 鉴定用于质体工程的高效叶绿体靶向肽。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-19 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002785
Chonprakun Thagun, Masaki Odahara, Yutaka Kodama, Keiji Numata

Plastids are pivotal target organelles for comprehensively enhancing photosynthetic and metabolic traits in plants via plastid engineering. Plastidial proteins predominantly originate in the nucleus and must traverse membrane-bound multiprotein translocons to access these organelles. This import process is meticulously regulated by chloroplast-targeting peptides (cTPs). Whereas many cTPs have been employed to guide recombinantly expressed functional proteins to chloroplasts, there is a critical need for more efficient cTPs. Here, we performed a comprehensive exploration and comparative assessment of an advanced suite of cTPs exhibiting superior targeting capabilities. We employed a multifaceted approach encompassing computational prediction, in planta expression, fluorescence tracking, and in vitro chloroplast import studies to identify and analyze 88 cTPs associated with Arabidopsis thaliana mutants with phenotypes linked to chloroplast function. These polypeptides exhibited distinct abilities to transport green fluorescent protein (GFP) to various compartments within leaf cells, particularly chloroplasts. A highly efficient cTP derived from Arabidopsis plastid ribosomal protein L35 (At2g24090) displayed remarkable effectiveness in chloroplast localization. This cTP facilitated the activities of chloroplast-targeted RNA-processing proteins and metabolic enzymes within plastids. This cTP could serve as an ideal transit peptide for precisely targeting biomolecules to plastids, leading to advancements in plastid engineering.

质体是通过质体工程全面提高植物光合作用和代谢特性的关键目标细胞器。质体蛋白主要来源于细胞核,必须穿过膜结合多蛋白转运体才能进入这些细胞器。这一导入过程受到叶绿体靶向肽(cTPs)的严格调控。虽然许多 cTPs 已被用于引导重组表达的功能蛋白进入叶绿体,但目前亟需更高效的 cTPs。在此,我们对一套先进的 cTPs 进行了全面的探索和比较评估,这些 cTPs 具有卓越的靶向能力。我们采用了包括计算预测、植物体表达、荧光跟踪和体外叶绿体导入研究在内的多方面方法,鉴定并分析了 88 种与拟南芥突变体相关的 cTPs,这些突变体具有与叶绿体功能相关的表型。这些多肽在将绿色荧光蛋白(GFP)转运到叶肉细胞内的各个区室,尤其是叶绿体方面表现出不同的能力。源自拟南芥质体核糖体蛋白 L35(At2g24090)的高效 cTP 在叶绿体定位方面表现出显著的功效。这种 cTP 促进了叶绿体靶向 RNA 处理蛋白和代谢酶在质体内的活动。这种 cTP 可作为一种理想的转运肽,将生物大分子精确定位到质体,从而推动质体工程学的发展。
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引用次数: 0
Promoting reusable and open methods and protocols (PRO-MaP) can improve methodological reporting in the life sciences. 推广可重复使用的开放式方法和规程(PRO-MaP)可以改进生命科学领域的方法报告。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-19 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002835
Sofia Batista Leite, Matthew A Brooke, Annamaria Carusi, Andy Collings, Pierre Deceuninck, Jean-François Dechamp, Bronwen Dekker, Elisa De Ranieri, Emma Ganley, Annalisa Gastaldello, Fanglian He, Marcel LaFlamme, Ingrid Langezaal, James Morris, David Pamies, Monica Piergiovanni, Bernd Pulverer, David Sadler, Caroline Shamu, Vivian Siegel, Marco Straccia, Tracey L Weissgerber

Detailed method descriptions are essential for reproducibility, research evaluation, and effective data reuse. We summarize the key recommendations for life sciences researchers and research institutions described in the European Commission PRO-MaP report.

详细的方法描述对于可重复性、研究评估和有效的数据再利用至关重要。我们总结了欧盟委员会 PRO-MaP 报告中为生命科学研究人员和研究机构提出的主要建议。
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引用次数: 0
A taxon-rich and genome-scale phylogeny of Opisthokonta. 富含类群和基因组规模的 Opisthokonta 系统发育。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-16 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002794
Hongyue Liu, Jacob L Steenwyk, Xiaofan Zhou, Darrin T Schultz, Kevin M Kocot, Xing-Xing Shen, Antonis Rokas, Yuanning Li

Ancient divergences within Opisthokonta-a major lineage that includes organisms in the kingdoms Animalia, Fungi, and their unicellular relatives-remain contentious. To assess progress toward a genome-scale Opisthokonta phylogeny, we conducted the most taxon rich phylogenomic analysis using sets of genes inferred with different orthology inference methods and established the geological timeline of Opisthokonta diversification. We also conducted sensitivity analysis by subsampling genes or taxa from the full data matrix based on filtering criteria previously shown to improve phylogenomic inference. We found that approximately 85% of internal branches were congruent across data matrices and the approaches used. Notably, the use of different orthology inference methods was a substantial contributor to the observed incongruence: analyses using the same set of orthologs showed high congruence of 97% to 98%, whereas different sets of orthologs resulted in somewhat lower congruence (87% to 91%). Examination of unicellular Holozoa relationships suggests that the instability observed across varying gene sets may stem from weak phylogenetic signals. Our results provide a comprehensive Opisthokonta phylogenomic framework that will be useful for illuminating ancient evolutionary episodes concerning the origin and diversification of the 2 major eukaryotic kingdoms and emphasize the importance of investigating effects of orthology inference on phylogenetic analyses to resolve ancient divergences.

Opisthokonta--一个包括动物界、真菌界及其单细胞近缘生物的主要类群--内部的古老分化仍然存在争议。为了评估建立基因组尺度 Opisthokonta 系统发生学的进展,我们使用不同的同源推断方法推断出的基因集进行了分类群最丰富的系统发生学分析,并建立了 Opisthokonta 多样化的地质年表。我们还进行了敏感性分析,根据以前证明可以改善系统发生推断的过滤标准,从完整数据矩阵中抽取基因或类群。我们发现,在不同的数据矩阵和所用的方法中,大约 85% 的内部分支是一致的。值得注意的是,使用不同的同源物推断方法是造成观察到的不一致的主要原因:使用同一套同源物进行的分析显示出高达 97% 至 98% 的一致性,而使用不同的同源物则导致较低的一致性(87% 至 91%)。对单细胞 Holozoa 关系的研究表明,在不同基因集中观察到的不稳定性可能源于微弱的系统发育信号。我们的研究结果提供了一个全面的Opisthokonta系统发生学框架,它将有助于揭示有关两大真核生物界起源和多样化的远古进化事件,并强调了研究系统发生学分析中同源推断的影响以解决远古分化问题的重要性。
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引用次数: 0
A new lineage nomenclature to aid genomic surveillance of dengue virus. 帮助登革热病毒基因组监测的新品系命名法。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-16 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002834
Verity Hill, Sara Cleemput, James Siqueira Pereira, Robert J Gifford, Vagner Fonseca, Houriiyah Tegally, Anderson F Brito, Gabriela Ribeiro, Vinicius Carius de Souza, Isabela Carvalho Brcko, Igor Santana Ribeiro, Iago Trezena Tavares De Lima, Svetoslav Nanev Slavov, Sandra Coccuzzo Sampaio, Maria Carolina Elias, Vi Thuy Tran, Duong Thi Hue Kien, Tuyen Huynh, Sophie Yacoub, Idrissa Dieng, Richard Salvato, Gabriel Luz Wallau, Tatiana S Gregianini, Fernanda M S Godinho, Chantal B F Vogels, Mallery I Breban, Mariana Leguia, Suraj Jagtap, Rahul Roy, Chanditha Hapuarachchi, Gaspary Mwanyika, Marta Giovanetti, Luiz C J Alcantara, Nuno R Faria, Christine V F Carrington, Kathryn A Hanley, Edward C Holmes, Wim Dumon, Alex Ranieri Jerônimo Lima, Tulio de Oliveira, Nathan D Grubaugh

Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here, we propose adding 2 sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present assignment tools to show that the proposed lineages are useful for regional, national, and subnational discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.

登革热病毒(DENV)目前正在地方病流行地区引发规模空前的流行病,并向新的地理区域扩展。因此,利用基因组监测追踪这种病毒至关重要。然而,病毒基因组多样性的复杂模式使现有的基因型分类系统难以使用。在此,我们建议增加 2 个亚基因型病毒分类级别,分别命名为主要系和次要系。这些系对系统发育距离和支系大小有较高的阈值,使它们在系统发育研究之间保持稳定。我们提出了一个赋值工具,以表明所提出的系对区域、国家和次国家级别的相关 DENV 多样性讨论非常有用。此外,所提出的世系在使用部分基因组序列进行分类时非常稳健。我们为 DENV 多样性提供了一个标准化的中性描述符,通过它我们可以识别和追踪具有潜在流行病学和/或临床重要性的系谱。有关我们的系谱系统的信息,包括为序列数据分配系谱和提出新系谱的方法,请访问:dengue-lineages.org。
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引用次数: 0
LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot. 依赖于 LXR 的增强子激活调节了肝脏对再进食反应的时间组织,导致致脂基因超调。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-06 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002735
Noga Korenfeld, Tali Gorbonos, Maria C Romero Florian, Dan Rotaro, Dana Goldberg, Talia Radushkevitz-Frishman, Meital Charni-Natan, Meirav Bar-Shimon, Carolyn L Cummins, Ido Goldstein

Transitions between the fed and fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) have not been explored. We examined the transcriptional and chromatin events occurring upon refeeding in mice, including kinetic behavior and molecular drivers. We found that the refeeding response is temporally organized with the early response focused on ramping up protein translation while the later stages of refeeding drive a bifurcated lipid synthesis program. While both the cholesterol biosynthesis and lipogenesis pathways were inhibited during fasting, most cholesterol biosynthesis genes returned to their basal levels upon refeeding while most lipogenesis genes markedly overshoot above pre-fasting levels. Gene knockout, enhancer dynamics, and ChIP-seq analyses revealed that lipogenic gene overshoot is dictated by LXRα. These findings from unbiased analyses unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.

哺乳动物在进食和禁食状态之间的转换很常见。肝脏通过转录调节能量利用和储存的代谢途径,协调对进食/禁食的适应性反应。目前尚未对停止禁食(再进食)后的转录和增强子动态进行研究。我们研究了小鼠断食后发生的转录和染色质事件,包括动力学行为和分子驱动因素。我们发现,进食反应在时间上是有组织的,早期反应主要集中在加速蛋白质翻译上,而进食后期则驱动一个分叉的脂质合成程序。虽然胆固醇生物合成和脂肪生成途径在禁食期间都受到抑制,但大多数胆固醇生物合成基因在进食后恢复到基础水平,而大多数脂肪生成基因则明显超过禁食前水平。基因敲除、增强子动力学和 ChIP-seq 分析表明,脂肪生成基因的超调是由 LXRα 决定的。这些无偏见的分析结果揭示了长期以来众所周知的进食脂肪超调现象背后的机制。
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引用次数: 0
Syllable processing is organized in discrete subregions of the human superior temporal gyrus. 人类颞上回的离散亚区组织了音节处理。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-06 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002774
Daniel R Cleary, Youngbin Tchoe, Andrew Bourhis, Charles W Dickey, Brittany Stedelin, Mehran Ganji, Sang Heon Lee, Jihwan Lee, Dominic A Siler, Erik C Brown, Burke Q Rosen, Erik Kaestner, Jimmy C Yang, Daniel J Soper, Seunggu Jude Han, Angelique C Paulk, Sydney S Cash, Ahmed M Raslan, Shadi A Dayeh, Eric Halgren

Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 μm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 μm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

约 1 毫米尺度的模块化组织可能是皮层处理的基础,但其在人类联想皮层中的存在尚不清楚。我们使用定制的高密度电极阵列放置在 7 名接受清醒开颅肿瘤切除术的患者的皮层表面,研究了人类左侧(优势)后颞上回的感受性言语处理。用间距为 200 μm 的 1,024 通道微网格记录的对辅音-元音音节和噪声编码对照的反应显示了直径约为 1.7 mm 的大致圆形区域,而在间距为 50 μm 的 128 通道线性阵列中则观察到了尖锐的边界,这可能与柱状组织一致。不同模块中音节的峰值潜伏期呈双峰分布,分别以 252 和 386 毫秒为中心。相邻模块之间的时间进程和刺激选择性截然不同。我们认为,接受语言皮层可能由离散的处理模块组成。
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引用次数: 0
Centrosome amplification primes ovarian cancer cells for apoptosis and potentiates the response to chemotherapy. 中心体扩增可使卵巢癌细胞凋亡并增强对化疗的反应。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-05 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002759
Frances Edwards, Giulia Fantozzi, Anthony Y Simon, Jean-Philippe Morretton, Aurelie Herbette, Andrea E Tijhuis, Rene Wardenaar, Stacy Foulane, Simon Gemble, Diana C J Spierings, Floris Foijer, Odette Mariani, Anne Vincent-Salomon, Sergio Roman-Roman, Xavier Sastre-Garau, Oumou Goundiam, Renata Basto

Centrosome amplification is a feature of cancer cells associated with chromosome instability and invasiveness. Enhancing chromosome instability and subsequent cancer cell death via centrosome unclustering and multipolar divisions is an aimed-for therapeutic approach. Here, we show that centrosome amplification potentiates responses to conventional chemotherapy in addition to its effect on multipolar divisions and chromosome instability. We perform single-cell live imaging of chemotherapy responses in epithelial ovarian cancer cell lines and observe increased cell death when centrosome amplification is induced. By correlating cell fate with mitotic behaviors, we show that enhanced cell death can occur independently of chromosome instability. We identify that cells with centrosome amplification are primed for apoptosis. We show they are dependent on the apoptotic inhibitor BCL-XL and that this is not a consequence of mitotic stresses associated with centrosome amplification. Given the multiple mechanisms that promote chemotherapy responses in cells with centrosome amplification, we assess such a relationship in an epithelial ovarian cancer patient cohort. We show that high centrosome numbers associate with improved treatment responses and longer overall survival. Our work identifies apoptotic priming as a clinically relevant consequence of centrosome amplification, expanding our understanding of this pleiotropic cancer cell feature.

中心体扩增是癌细胞的一个特征,与染色体不稳定性和侵袭性有关。通过中心体解聚和多极分裂增强染色体的不稳定性和随后的癌细胞死亡是一种目标明确的治疗方法。在这里,我们发现中心体扩增除了对多极分裂和染色体不稳定性有影响外,还能增强对传统化疗的反应。我们对上皮性卵巢癌细胞系的化疗反应进行了单细胞活体成像,观察到中心体扩增诱导的细胞死亡增加。通过将细胞命运与有丝分裂行为相关联,我们发现细胞死亡的增加可能与染色体不稳定性无关。我们发现,中心体扩增的细胞开始凋亡。我们证明它们依赖于凋亡抑制剂 BCL-XL,而这并不是中心体扩增相关的有丝分裂压力的结果。鉴于促进中心体扩增细胞化疗反应的多种机制,我们在上皮性卵巢癌患者队列中评估了这种关系。我们发现,中心体数量多与治疗反应改善和总生存期延长有关。我们的研究确定了中心体扩增的临床相关后果--凋亡启动,从而拓展了我们对这一多向性癌细胞特征的认识。
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引用次数: 0
Keeping time: How musical training may boost cognition. 保持时间音乐训练如何提高认知能力
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-05 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002810
M Florencia Assaneo, Fernando Lizcano-Cortés, Pablo Ripolles

The relationship between musical training and intellect is controversial. A new hypothesis may help resolve the debate by proposing an explanation for how training in rhythmic skills can improve cognitive abilities in some individuals, but not others.

音乐训练与智力之间的关系存在争议。一个新的假说可能有助于解决这一争论,它提出了一个解释,即节奏技能训练为何能提高某些人的认知能力,而不是其他人。
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引用次数: 0
A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits. paxillin LIM3 结构域中的柔性环介导其与整合素 β 亚基的直接结合。
IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-09-04 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002757
Timo Baade, Marcus Michaelis, Andreas Prestel, Christoph Paone, Nikolai Klishin, Marleen Herbinger, Laura Scheinost, Ruslan Nedielkov, Christof R Hauck, Heiko M Möller

Integrins are fundamental for cell adhesion and the formation of focal adhesions (FA). Accordingly, these receptors guide embryonic development, tissue maintenance, and haemostasis but are also involved in cancer invasion and metastasis. A detailed understanding of the molecular interactions that drive integrin activation, FA assembly, and downstream signalling cascades is critical. Here, we reveal a direct association of paxillin, a marker protein of FA sites, with the cytoplasmic tails of the integrin β1 and β3 subunits. The binding interface resides in paxillin's LIM3 domain, where based on the NMR structure and functional analyses, a flexible, 7-amino acid loop engages the unstructured part of the integrin cytoplasmic tail. Genetic manipulation of the involved residues in either paxillin or integrin β3 compromises cell adhesion and motility of murine fibroblasts. This direct interaction between paxillin and the integrin cytoplasmic domain identifies an alternative, kindlin-independent mode of integrin outside-in signalling particularly important for integrin β3 function.

整合素是细胞粘附和形成病灶粘附(FA)的基础。因此,这些受体引导胚胎发育、组织维护和止血,但也参与癌症的侵袭和转移。详细了解驱动整合素激活、FA 组装和下游信号级联的分子相互作用至关重要。在这里,我们揭示了 FA 位点标记蛋白 paxillin 与整合素 β1 和 β3 亚基胞质尾部的直接关联。根据核磁共振结构和功能分析,结合界面位于 paxillin 的 LIM3 结构域,其中一个灵活的 7 氨基酸环与整合素细胞质尾部的非结构化部分结合。对 paxillin 或整合素 β3 中的相关残基进行遗传操作会影响小鼠成纤维细胞的细胞粘附性和运动性。paxillin 与整合素胞质结构域之间的这种直接相互作用确定了整合素外-内信号传导的另一种独立于 kindlin 的模式,这种模式对整合素 β3 的功能尤为重要。
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引用次数: 0
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