An Intercellular Connection in Endospore Development

内生孢子发育中的细胞间连接

• 批准号: 9269236
• 负责人: Charles P. Moran
• 金额: $ 29.64万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9269236
• 关键词: Address; Amino Acid Substitution; Antibiotic Resistance; Antibiotics; Appearance; Bacillus anthracis; Bacillus cereus; Bacillus subtilis; Bacteria; Bacterial Infections; Biological Models; Cell Differentiation process; Cell Membrane Proteins; Cell membrane; Cells; Cellular biology; Chemicals; Clostridium difficile; Communication; Complex; Cytoplasm; DNA-Directed RNA Polymerase; Development; Disinfectants; Employee Strikes; Environment; F Factor; Fluorescence Resonance Energy Transfer; Gene Expression; Gene Expression Regulation; Genes; Goals; Health; Host Defense; Human; Knowledge; Location; Membrane; Mission; Modeling; Molecular; Mothers; Multiprotein Complexes; Mutagenesis; N-Acetylmuramoyl-L-alanine Amidase; Phagocytes; Proteins; Public Health; Recruitment Activity; Reproduction spores; Research; Resistance; Role; Siblings; Sigma Factor; Signal Transduction; Specificity; Structural Models; System; Testing; Transducers; United States National Institutes of Health; cell type; combat; crosslink; design; improved; in vivo; intercellular connection; intracellular protein transport; novel; novel strategies; pathogen; promoter; protein complex; public health relevance

DESCRIPTION (provided by applicant): Many bacteria build specialized differentiated cells in order to survive environmental insults, to disseminate in the environment, and to resist host defenses, antibiotics and disinfectants. A striking example of this type of cell differentiation by many important bacterial pathogens is the formation of endospores (e.g., Bacillus anthracis, Bacillus cereus, Clostridium difficile). Our overall goal is to understand the special molecular mechanisms that guide the development of endospores in order to identify novel targets for disrupting spore development. We will exploit the model system of endospore development in Bacillus subtilis because this system is amenable to analysis and its study has led to the discovery of many mechanisms that control gene expression in most bacteria, including pathogens. In this proposal we focus on the roles of a protein complex that connects two cells during endospore development. Early after the onset of endospore formation the cell divides asymmetrically giving rise to two dissimilar sibling cells. One of these cells (the forespore) develops into the endospore, while the other (the mother cell) becomes a terminally differentiated cell that nurtures the developing endospore. Remarkably, gene expression is coordinated between the forespore and mother cell (e.g., expression of specific genes in the mother cell is required before a subsequent set of genes is expressed in the forespore). The communication between the mother cell and forespore depends upon the targeting of several groups of proteins to the interface between the mother cell and forespore. The mechanisms for subcellular localization of specific proteins are of fundamental importance in cell biology and development. The central questions to be addressed in this proposal are how are specific proteins localized to the interface between the mother cell and forespore, and what are their functions. The two key proteins in this study, SpoIIQ and SpoIIIAH, interact through two membranes to connect the forespore and the mother cell. The SpoIIQ-SpoIIIAH complex serves as the founder that marks the membrane interface between the forespore and mother cell for the recruitment of other proteins to this subcellular location, including peptidoglycan hydrolases that function during the phagocytic-like engulfment of the forespore membrane by the mother cell membrane, proteins required for signaling from the forespore to the activate mother cell gene expression, and mother-cell proteins required for gene expression in the forespore. Moreover, the SpoIIQ-SpoIIIAH complex appears to form a new type of channel or transporter that connects the mother cell and forespore cytoplasms. The specific aims of this proposal are designed to identify which and how other proteins are recruited to this intercellular connection, and how these protein complexes function to coordinate gene expression between the two cells.

描述（由申请人提供）：许多细菌建立了专门的分化细胞，以生存环境侮辱，在环境中传播并抵抗宿主防御，抗生素和消毒剂。通过 许多重要的细菌病原体是内生孢子的形成（例如炭疽芽孢杆菌，熟食芽孢杆菌，艰难梭菌）。我们的总体目标是了解指导内生孢子发展的特殊分子机制，以确定破坏孢子发育的新目标。我们将利用枯草芽孢杆菌中内孢子发育的模型系统，因为该系统可适应分析，其研究导致发现了许多机制，这些机制控制了大多数细菌（包括病原体）中基因表达的许多机制。 在此提案中，我们着重于在内孢子发育过程中连接两个细胞的蛋白质复合物的作用。内孢子形成发作后的早期，细胞不对称地划分为两个不同的同胞细胞。这些细胞之一（前孔）发展成内孢子，而另一个细胞（母细胞）变成了一个终极分化的细胞，可以培育发育中的内孢子。值得注意的是，基因表达在前孔和母细胞之间协调（例如，在前孔中表达后续基因之前，需要在母细胞中的特定基因表达）。母细胞和前孔之间的通信取决于将几组蛋白质靶向到母细胞和前孔之间的界面。特定蛋白质亚细胞定位的机制在细胞生物学和发育中至关重要。该提案中要解决的主要问题是如何将特定的蛋白质定位于母细胞和前孔之间的接口，以及它们的功能是什么。这项研究的两个关键蛋白Spoiiq和Spoiiiah通过两个膜相互作用，连接前孔和母细胞。 Spoiiq-Spoiiiah复合体是创始人，标记了前孔和母细胞之间的膜接口，以募集其他蛋白质到该亚细胞位置，包括在吞噬膜细胞中的吞噬细胞类似物的吞噬症状及其表演者的吞噬性吞吐量，这些水解酶在吞噬细胞中起作用，用于吞噬吞噬细胞的吞吐量，以表产生母细胞素，以表产生蛋白质，以表产生蛋白质，以表产生蛋白质的表现力和表达性，这些蛋白会激活的表演者及其表演型的表达性，这些蛋白会在膜片上进行表演，以供表演型膜膜膜，以使蛋白质的表现量繁殖。母细胞蛋白在前孔中需要基因表达。此外，Spoiiq-Spoiiiah复合物似乎形成了连接母细胞和前孔细胞肿瘤的新型通道或转运蛋白。该提案的具体目的旨在确定其他蛋白质如何募集到该细胞间连接，以及这些蛋白质复合物如何在两个细胞之间进行基因表达来协调基因表达。