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: 8986795
• 负责人: Thomas James Melia
• 金额: $ 35.24万
• 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/8986795
• 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; Health; 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; biophysical techniques; flexibility; novel; pathogen; protein aggregate; 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）：宏观噬菌是细胞内应力 - 响应途径，细胞包装部分的细胞包装部分输送到溶酶体中。这种“包装”是通过从头形成的新细胞器来进行的，称为自噬体，该细胞器生长并封装了最终溶酶体降解的胞质材料。自噬体如何形成，尤其是膜如何扩展并最终关闭自身是一项激烈的研究领域。与这些活动有关的一个因素是泛素样蛋白ATG8。在自噬过程中，ATG8在脑胶质体膜上共价与磷脂酰乙醇胺（PE）结合，并通过自噬体的成熟过程保持结合。我们的初步结果表明，ATG8-PE是将膜变形的核心数字，这可能是确定膜束缚或膜融合的位点的前奏。在这里，我们将基于这些结果来确定ATG8如何控制自噬体成熟后期步骤的每个膜动力学。