SNAREs mediate ER-vesicle fusion on Legionella Vacuoles

SNARE 介导军团菌液泡上的 ER-囊泡融合

• 批准号: 6885556
• 负责人: MARY-PAT STEIN
• 金额: $ 5.15万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885556
• 关键词: Legionella; bacteria infection mechanism; bacterial cytopathogenic effect; bacterial proteins; biological transport; cell membrane; confocal scanning microscopy; endoplasmic reticulum; gel electrophoresis; host organism interaction; immunoprecipitation; membrane fusion; postdoctoral investigator; transport proteins; vesicle /vacuole

DESCRIPTION (provided by applicant): Legionella pneumophila is a gram-negative bacteria that utilizes a type IV secretion system to alter its intracellular trafficking in host macrophages. Internalized Legionella containing vacuoles (LCV) immediately avoid transport to lysosomes and within 15 minutes of internalization, begin remodeling their phagosomal compartment with ER-derived host cell vesicles. Dot/icm mutants are efficiently transported to and fuse with lysosomes suggesting that the type IV secretion apparatus is required for altered LCV trafficking and remodeling. Identification of factors utilized by Legionella to alter trafficking and remodel its intracellular vacuole may provide new targets for therapeutic intervention. Furthermore, understanding how ER-derived vesicles are recruited to and fuse with a membrane-bound compartment originating from the plasma membrane may provide insight into novel host cell functions. Confocal microscopy, coimmunprecipitation studies, 2D-gel electrophoresis and in vitro budding and fusion reactions will be used to identify host and/or Legionella derived SNARE-like molecules that play a role in ER-derived vesicle fusion with LCV.

描述（由申请人提供）：肺炎军团菌是一种革兰氏阴性细菌，利用IV型分泌系统改变其细胞内贩运在宿主巨噬细胞中。含有液泡的内部化军团菌（LCV）立即避免运输到溶酶体，并在内在化的15分钟内开始使用ER衍生的宿主细胞囊泡重塑其吞噬室。 DOT/ICM突变体有效地运输到并与溶酶体融合，这表明IV型分泌设备需要改变LCV运输和重塑。识别军团菌利用的因素来改变贩运和重塑其细胞内液泡可能为治疗干预提供新的靶标。此外，了解如何将源自源的囊泡募集到源自质膜的膜结合室并融合，这可能会提供对新型宿主细胞功能的见解。共聚焦显微镜，共发育研究，2D-GEL电泳以及体外萌芽和融合反应将用于鉴定在与LCV的ER衍生小囊泡融合中起作用的宿主和/或Legionelly衍生的类似的类似的蜂蜜样分子。