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: 8598911
• 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/8598911
• 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; biophysical techniques; 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(申请人提供)：宏自噬是细胞内的应激反应途径，细胞通过该途径包装部分胞质以输送到溶酶体中。这种“包装”是由一种名为自噬小体的新细胞器的从头形成进行的，该细胞器生长并包裹胞浆物质，以供最终溶酶体降解。自噬小体是如何形成的，特别是膜是如何膨胀并最终关闭的，这是一个需要深入研究的领域。参与这些活动的一个因素是泛素样蛋白Atg8。在自噬过程中，ATG8与自噬前膜上的磷脂酰乙醇胺(PE)共价结合，并通过自噬小体的成熟过程保持结合。我们的初步结果表明，Atg8-PE是膜变形的中心角色，可能是确定膜系留或膜融合位置的前奏。在这里，我们将以这些结果为基础，确定Atg8如何控制自噬体成熟后期步骤下的每一种膜动力学。