Molecular mechanisms initiating cell migrations in Caonorhabditis elegans

秀丽隐杆线虫细胞迁移的分子机制

• 批准号: 10796184
• 负责人: Martha C Soto
• 金额: $ 15.57万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10796184
• 关键词: Actins; Address; Adhesions; Apical; Biological Markers; Cadherins; Caenorhabditis elegans; Cancer Etiology; Cell membrane; Cell physiology; Cells; Cellular biology; Cicatrix; Colon Carcinoma; Complex; Cues; Cytoskeleton; Development; Developmental Process; Disease; Elements; Epidermis; F-Actin; Genes; Guanosine Triphosphate Phosphohydrolases; Health; Homologous Gene; Human; Image; Life; Malignant Neoplasms; Malignant neoplasm of prostate; Membrane; Molecular; Movement; Mutate; Neoplasm Metastasis; Neurons; Pattern; Process; Public Health; Regulation; Signal Transduction; System; Tissues; cell motility; clinically relevant; developmental disease; extracellular; human disease; insight; model organism; neurodevelopment; neuron development; novel; polarized cell; receptor; recruit; trafficking; transmission process; triple-negative invasive breast carcinoma

Molecular mechanisms initiating cell migrations Project Summary/Abstract The process by which extracellular signals act through receptors at the plasma membrane to influence cell function is a fundamental requirement for life. Cytoskeletal elements, including branched actin, transmit signals throughout the cell. When branched actin is not properly polarized this can result in serious health problems like defective neuronal development or cancer metastases. We study how the actin cytoskeleton interprets extracellular signals to carry out polarized functions, including polarized cell migrations and polarized intracellular trafficking. We established a genetically amenable system in which signaling to specific tissues can be analyzed. Our system also identifies the relevant signals that promote specific developmental processes, uncovers novel components contributing to the propagation of the signal, and uses live imaging to provide insights into the cell biology controlled by the signals. Previously we identified and characterized three signals that pattern membrane recruitment of the GTPase Rac1/CED-10, which in turn recruit the branched actin regulator WAVE/Scar to regulate the dynamics of F-actin during a cell migration. Now we are ready to address: 1) How does branched actin promote the Cadherin trafficking that sets up proper apical/basal polarity? 2) Which Rac GEF(s) specifically convert signals received by the epidermis into epidermal motility cues? 3) How does branched-actin-dependent adhesion support tissuetissue movements? Clinical relevance: The human homolog of one of the genes we study in C. elegans, WAVE3, is considered a biomarker for high grade, triple negative breast cancer (Kulkarni et al., 2012) and is associated with invasive prostate and colon cancers (Fernando et al., 2010; Zhang et al., 2012). Understanding the signals that regulate actin dynamics through the WAVE/Scar complex during cell migrations will suggest new biomarkers for altered actin regulation in human disease.

启动细胞迁移的分子机制 项目总结/摘要 细胞外信号通过质膜上的受体影响细胞的过程 功能是生命的基本要求。细胞骨架成分，包括分支肌动蛋白， 整个细胞。当分支肌动蛋白没有正确极化时，这可能导致严重的健康问题 比如神经发育缺陷或癌症转移。我们研究肌动蛋白细胞骨架如何解释 细胞外信号进行极化功能，包括极化细胞迁移和极化 细胞内运输我们建立了一个遗传上可接受的系统，在这个系统中， 可以分析。我们的系统还识别了促进特定发展的相关信号。 处理，发现有助于信号传播的新组件，并使用实时成像， 提供了对信号控制的细胞生物学的见解。之前我们鉴定并表征了三种 信号，图案膜募集的GTCRac 1/CED-10，这反过来又招募分支 肌动蛋白调节因子WAVE/Scar在细胞迁移过程中调节F-肌动蛋白的动力学。现在我们准备 地址：1）分支肌动蛋白如何促进钙粘蛋白的运输，建立适当的顶端/基底 极性？2)哪些Rac GEF特异性地将表皮接收的信号转化为表皮运动性 线索？3)分支肌动蛋白依赖性粘附是如何支持组织运动的？临床 相关性：我们在C中研究的一个基因的人类同源物。elegans，WAVE 3，被认为是一种 高级别、三阴性乳腺癌的生物标志物（Kulkarni等人，2012年），并与侵入性 前列腺癌和结肠癌（Fernando等，2010; Zhang等人，2012年）。了解调节的信号 在细胞迁移过程中通过WAVE/Scar复合体的肌动蛋白动力学将为改变的细胞迁移提供新的生物标志物。 肌动蛋白在人类疾病中的调节。

项目成果

WAVE facilitates polarized E-cadherin transport.

• DOI: 10.1091/mbc.e22-08-0322
• 发表时间: 2023-05-01
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Cordova-Burgos L;Rao D;Egwuonwu J;Borinskaya S;Sasidharan S;Soto M
• 通讯作者: Soto M

WAVE regulates Cadherin junction assembly and turnover during epithelial polarization.

WAVE 在上皮极化过程中调节钙粘蛋白连接的组装和周转。

• DOI: 10.1016/j.ydbio.2017.12.002
• 发表时间: 2018
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Sasidharan,Shashikala;Borinskaya,Sofya;Patel,Falshruti;Bernadskaya,Yelena;Mandalapu,Sailaja;Agapito,Maria;Soto,MarthaC
• 通讯作者: Soto,MarthaC

The branched actin nucleator Arp2/3 promotes nuclear migrations and cell polarity in the C. elegans zygote.

• DOI: 10.1016/j.ydbio.2011.07.008
• 发表时间: 2011-09-15
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Xiong H;Mohler WA;Soto MC
• 通讯作者: Soto MC

WAVE/SCAR promotes endocytosis and early endosome morphology in polarized C. elegans epithelia.

• DOI: 10.1016/j.ydbio.2013.03.012
• 发表时间: 2013-05-15
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Patel, Falshruti B.;Soto, Martha C.
• 通讯作者: Soto, Martha C.

The WAVE/SCAR complex promotes polarized cell movements and actin enrichment in epithelia during C. elegans embryogenesis.

• DOI: 10.1016/j.ydbio.2008.09.023
• 发表时间: 2008-12-15
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Patel, Falshruti B.;Bernadskaya, Yelena Y.;Chen, Esteban;Jobanputra, Aesha;Pooladi, Zahra;Freeman, Kristy L.;Gally, Christelle;Mohler, William A.;Soto, Martha C.
• 通讯作者: Soto, Martha C.