Identifying Genes that Function in a Novel Signaling Pathway that Controls both Cell Adhesion and Initial Cell Fate Specification

识别在控制细胞粘附和初始细胞命运规范的新型信号通路中起作用的基因

• 批准号: 0444883
• 负责人: Daphne Blumberg
• 金额: --
• 依托单位: University of Maryland Baltimore County
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0444883&HistoricalAwards=false
• 关键词: Identifying; Genes; Function; Novel; Signaling

A protein sharing homology with anti-coaggulants known to competitively inhibit integrin receptor binding to fibrinogen has been described in a protist, Dictyostelium discoideum. This protein, AmpA, functions as a novel signaling molecule that plays both autocrine and paracrine roles controlling cell adhesion and cell fate specification during growth and development. Dictyostelium is a model system extensively used to study cell migration and development. AmpA functions to reduce cell-cell and cell-substrate adhesion, promoting migration of these cells facilitating their ability to forage for food. During the developmental phase of the life cycle the expression of the ampA gene is restricted to a small, but highly motile subset of cells whose migrations are necessary for proper morphogenesis. AmpA expression is essential for migration of these cells. It also acts as a lateral inhibitory signal that prevents adjacent cells from assuming a prespore fate. The simplest model for AmpA function is that it is a modulator of an integrin like receptor. Integrin receptors, however, have not been identified outside of metazoan organisms and there is no obvious integrin receptor that can be identified by sequence homology in Dictyostelium. The objective of this project is to identify the adhesion receptor that is modulated by interaction with the AmpA protein and to identify additional genes that are candidates to function in the AmpA modulated signaling pathway. Aim 1: will use biochemical and molecular genetic approaches to identify and characterize the receptor to which AmpA binds. Aim 2: will use a genetic approach, isolation of second site suppressor mutations, to identify additional genes that function in the AmpA mediated signal transduction pathways. Using AmpA as a probe to identify the adhesion receptors that are modulated by its action and to identify other genes that function downstream in the AmpA signaling pathway should help to elucidate the nature of cell-substrate adhesion and its modulation to promote cell migration and provide insight to how the metozoan integrin paradigm evolved. It should be noted that this project will involve graduate and undergraduate students, some of whom are members of under represented minorities. The research experience gained working on this project will contribute to their scientific education.

与抗凝集剂的蛋白质共享同源物已在原生dictyostelium discoideum中描述了竞争性抑制整联蛋白受体与纤维蛋白原结合的蛋白质。该蛋白AMPA充当一种新型信号分子，在生长和发育过程中扮演着控制细胞粘附和细胞命运规范的自分泌和旁分泌作用。 Dictyostelium是一种广泛用于研究细胞迁移和发育的模型系统。 AMPA的功能可减少细胞细胞和细胞基底粘附，促进这些细胞的迁移，促进其觅食能力。在生命周期的发展阶段，AMPA基因的表达仅限于细胞的小但高度运动的子集，其迁移对于正确形态发生是必需的。 AMPA表达对于这些细胞的迁移至关重要。它也充当横向抑制信号，可防止相邻细胞假设命运。 AMPA函数的最简单模型是它是整联蛋白之类的受体的调节剂。然而，整合素受体尚未被鉴定在后生动物的生物之外，并且没有明显的整联蛋白受体可以通过dictyostelium中的序列同源性鉴定。该项目的目的是确定通过与AMPA蛋白相互作用调节的粘附受体，并确定在AMPA调制信号通路中起作用的其他基因。目标1：将使用生化和分子遗传方法识别和表征AMPA结合的受体。目标2：将使用遗传方法，分离第二位点抑制剂突变，以识别在AMPA介导的信号转导途径中起作用的其他基因。使用AMPA作为探针来识别其作用调节的粘附受体，并鉴定在AMPA信号通路中下游发挥作用的其他基因，应有助于阐明细胞覆盖粘附的性质及其调节，以促进细胞迁移，并为如何洞悉Metosoan gyleosoan intemin intemin paradigm paradigm paradigm paradigm。应当指出的是，该项目将涉及毕业生和本科生，其中一些人是代表少数群体的成员。从事该项目的研究经验将有助于他们的科学教育。