Regulation of Autophagosome Membrane Dynamics by the AtgB Family of Proteins

描述（由申请人提供）：宏观自噬是细胞内的应激反应途径，通过该途径，细胞将部分细胞质包装以传递到溶酶体中。这种“包装”是由一种叫做自噬体的新细胞器的重新形成来完成的，自噬体生长并包裹胞质物质，最终用于溶酶体的降解。自噬体是如何形成的，特别是膜是如何膨胀并最终自我关闭的，这是一个深入研究的领域。与这些活性有关的一个因素是泛素样蛋白at8。在自噬过程中，at8在自噬体前膜上与磷脂酰乙醇胺（PE）共价结合，并在自噬体成熟过程中保持这种结合。我们的初步结果表明，Atg8-PE是膜变形的核心人物，可能是确定膜系扣或膜融合位点的前奏。在这里，我们将建立在这些结果的基础上，以确定at8如何控制每个膜动力学，这些膜动力学是自噬体成熟后期步骤的基础。

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.