Regulation of Growth to Differentiation Transitions

生长向分化转变的调节

• 批准号: 7458832
• 负责人: ADAM KUSPA
• 金额: $ 25.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7458832
• 关键词: ATP-Binding Cassette Transporters; Amino Acids; Biochemical; Biological; Biological Assay; Cell Cycle Stage; Cell Differentiation process; Cell membrane; Cells; Complex; Defect; Development; Dictyostelium; Dictyostelium discoideum; Dissection; Epitopes; Eukaryota; Eukaryotic Cell; Genes; Genetic; Genetic Screening; Growth; Homologous Gene; In Vitro; Individual; Link; Location; Maintenance; Malignant Neoplasms; Measurement; Methods; Modeling; Molecular; Molecular Genetics; Pathway interactions; Peptides; Phenotype; Physiological; Process; Property; Protein Binding; Protein Kinase; Proteins; Regulation; Role; Signal Pathway; Signal Transduction; Specific qualifier value; Suppressor Mutations; System; Testing; Tissues; Transport Reaction; Vesicle; Work; cell growth; cell type; efflux pump; human disease; improved; mutant; receptor; reconstitution; research study; response; tool

DESCRIPTION (provided by applicant): The long-term objectives of this project are to define the cellular regulatory mechanisms that govern cell differentiation in eukaryotes using Dictyostelium discoideum as a model. This system can be used to provide a complete picture of a significant biological problem: the integration of individual cells into a multicellular tissue with the proper form and function. Several components of the regulatory network that govern the growth to development transition in this system have been characterized, including the putative receptor/protein kinases Gdt2 and Gdt9 and the ABC transporters TagA and AbcGl 1. These four regulators are critical links in the regulatory network that controls growth, the decision to initiate development and initial establishment of specific cell types. Specific hypotheses will be tested in an effort to determine their functions at a mechanistic level. Each of the proteins are critical nodes within new signaling pathways and studying them may illuminate regulatory systems that are fundamental to all eukaryotes. The function of these signaling pathways will be studied by genetic, molecular genetic, cell biological and physiological methods. New protein components of these pathways will be uncovered in several genetic screens. The function of these new components will be explored by examining mutant phenotypes, direct biochemical measurements of their function and other physiological properties. Describing complex biological pathways is the result of integrating information on many individual components and on their interactions. This is most easily done in relatively simple systems such as Dictyostelium that afford the use of powerful molecular tools. The results will improve our understanding of the cellular acquisition and maintenance of the differentiated state in eukaryotes. Thus, this work should impact our ability to treat human diseases caused by defects in cellular growth control, such as cancer.

描述（由申请人提供）： 本项目的长期目标是以盘基网柄藻为模型，确定真核生物细胞分化的细胞调控机制。这个系统可以用来提供一个重要的生物学问题的全貌：将单个细胞整合成具有适当形式和功能的多细胞组织。已经表征了在该系统中控制生长向发育转变的调控网络的几个组分，包括推定的受体/蛋白激酶Gdt 2和Gdt 9以及ABC转运蛋白TagA和AbcGll。这四个调节器是控制生长的调节网络中的关键环节，决定启动特定细胞类型的发育和初步建立。具体的假设将进行测试，以确定其功能在一个机械水平。每一种蛋白质都是新信号通路中的关键节点，研究它们可能会阐明所有真核生物的基本调控系统。这些信号通路的功能将通过遗传学、分子遗传学、细胞生物学和生理学方法进行研究。这些途径的新蛋白质组分将在几个遗传筛选中被发现。将通过检查突变表型、对其功能和其他生理特性的直接生化测量来探索这些新成分的功能。描述复杂的生物学途径是整合许多单个组件及其相互作用信息的结果。这在相对简单的系统中最容易完成，例如提供使用强大的分子工具的网骨藻。这些结果将有助于我们更好地理解真核生物中细胞获得和维持分化状态的过程。因此，这项工作应该会影响我们治疗由细胞生长控制缺陷引起的人类疾病（如癌症）的能力。

项目成果

CulB, a putative ubiquitin ligase subunit, regulates prestalk cell differentiation and morphogenesis in Dictyostelium spp.

CulB 是一种假定的泛素连接酶亚基，可调节盘基网柄菌属的前茎细胞分化和形态发生。

• DOI: 10.1128/ec.1.1.126-136.2002
• 发表时间: 2002
• 期刊: Eukaryotic cell
• 作者: Wang,Bin;Kuspa,Adam
• 通讯作者: Kuspa,Adam

Integrated maps of the chromosomes in Dictyostelium discoideum.

盘基网柄菌染色体的整合图谱。

• DOI: 10.1093/genetics/141.1.147
• 发表时间: 1995
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Loomis,WF;Welker,D;Hughes,J;Maghakian,D;Kuspa,A
• 通讯作者: Kuspa,A

Transcriptional down-regulation and rRNA cleavage in Dictyostelium discoideum mitochondria during Legionella pneumophila infection.

嗜肺军团菌感染期间盘基网柄菌线粒体中的转录下调和 rRNA 裂解。

• DOI: 10.1371/journal.pone.0005706
• 发表时间: 2009-05-27
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Zhang C;Kuspa A
• 通讯作者: Kuspa A

Two-component signal transduction systems in eukaryotic microorganisms.

• DOI: 10.1016/s1369-5274(98)80109-4
• 发表时间: 1998-12
• 期刊: Current opinion in microbiology
• 影响因子: 5.4
• 作者: William F. Loomis;A. Kuspa;G. Shaulsky

A novel partner for Dictyostelium filamin is an alpha-helical developmentally regulated protein.

盘基网柄菌丝蛋白的新伙伴是一种α螺旋发育调节蛋白。

• DOI: 10.1242/jcs.01366
• 发表时间: 2004
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Knuth,Monika;Khaire,Nandkumar;Kuspa,Adam;Lu,SiJie;Schleicher,Michael;Noegel,AngelikaA
• 通讯作者: Noegel,AngelikaA