Regulation of Autophagosome Membrane Dynamics by the AtgB Family of Proteins

AtgB 蛋白家族对自噬体膜动力学的调节

• 批准号: 8435915
• 负责人: Thomas James Melia
• 金额: $ 35.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8435915
• 关键词: Amino Acid Sequence; Architecture; Area; Autophagocytosis; Autophagosome; Binding; Binding Proteins; Biochemical; Biological Assay; Cell model; Cells; Coupling; Cytosol; Dependence; Encapsulated; Event; Family; Growth; Homo; In Vitro; Ligase; Lipids; Liposomes; Lumen of the Lysosome; Lysosomes; Maps; Measures; Mediating; Membrane; Membrane Fusion; Membrane Proteins; Nutrient; Organelles; Pathway interactions; Peptide Sequence Determination; Phosphatidylethanolamine; Physiological; Population; Process; Protein Family; Proteins; Reaction; Regulation; Role; Site; Staging; Starvation; Structure; Surface; System; Testing; Ubiquitin Like Proteins; Uncertainty; Vesicle; Yeasts; base; biological adaptation to stress; flexibility; novel; pathogen; protein aggregate; public health relevance; reconstitution; response; stressor; trafficking

DESCRIPTION (provided by applicant): Macro-autophagy is the intracellular stress-response pathway by which the cell packages portions of the cytosol for delivery into the lysosome. This "packaging" is carried out by the de novo formation of a new organelle called the autophagosome that grows and encapsulates cytosolic material for eventual lysosomal degradation. How autophagosomes form, including especially how the membrane expands and eventually closes upon itself is an area of intense study. One factor implicated in these activitie is the ubiquitin-like protein, Atg8. During autophagy, Atg8 becomes covalently bound to phosphatidylethanolamine (PE) on the preautophagosomal membrane and remains bound through the maturation process of the autophagosome. Our preliminary results suggest that Atg8-PE is a central figure in deforming the membrane perhaps as a prelude to determining sites of membrane tethering or membrane fusion. Here we will build on these results to determine how Atg8 might control each of the membrane dynamics that underlie the late steps of autophagosome maturation.

描述（由申请人提供）：大自噬是细胞内应激反应途径，细胞通过该途径包装部分细胞溶质以递送到溶酶体中。这种“包装”是通过一种新的细胞器的从头形成来进行的，这种细胞器被称为自噬体，自噬体生长并包裹胞质物质以最终降解溶酶体。自噬体是如何形成的，尤其是细胞膜如何扩张并最终自我封闭，这是一个深入研究的领域。参与这些活动的一个因子是泛素样蛋白Atg 8。在自噬过程中，Atg 8与前自噬体膜上的磷脂酰乙醇胺（PE）共价结合，并在自噬体成熟过程中保持结合。我们的初步结果表明，Atg 8-PE是一个中心人物在变形的膜可能作为一个前奏，以确定网站的膜系留或膜融合。在这里，我们将建立在这些结果，以确定如何Atg 8可能控制每一个膜动力学的基础上的自噬体成熟的后期步骤。