Receptor dynamics, internalization and retrograde transport of a viral A/B toxin in yeast and in mammalian cells

内吞作用是真核细胞内化其细胞表面的部分以去除质膜蛋白以控制多种生物过程（包括细胞信号传导、增殖、分化、存活和迁移）的必要过程。在受体介导的内吞作用中，受体/配体复合物通常快速内化并通过早期和/或晚期内体递送至最终靶区室。尽管对参与这一基本细胞过程的单个组分进行了深入研究，但对导致受体介导的内吞作用和细胞内货物运输的潜在动态原理知之甚少。本项目旨在解决这些根本上重要的和密切相关的过程相结合的实验数据与理论建模，以表征肌动蛋白依赖的受体内吞作用和细胞内贩运的细胞H/KDEL受体Erd 2 p和它的病毒A/B毒素配体在酵母和哺乳动物细胞。一个主要的目标将是联合收割机数学建模与遗传，生物化学和活细胞成像数据，以开发一个理论模型，描述和预测受体/配体相互作用和胞吞内化/贩运步骤更精确和一般的情况下。

Endocytosis is an essential process by which eukaryotic cells internalize portions of their cell surface to remove plasma membrane proteins in order to control a variety of biological processes including cell signaling, proliferation, differentiation, survival and migration. In receptor-mediated endocytosis, receptor/ligand complexes are usually rapidly internalized and delivered to the final target compartment via early and/or late endosomes. Despite intensive studies on individual components involved in this basic cellular process, the underlying dynamic principles resulting in receptor-mediated endocytosis and intracellular cargo trafficking are only poorly understood. The present project intends to address these fundamentally important and closely interconnected processes by combining experimental data with theoretical modeling to characterize actin-dependent receptor-endocytosis and intracellular trafficking of the cellular H/KDEL receptor Erd2p and its viral A/B toxin ligand in yeast and in mammalian cells. A major goal will be to combine mathematical modeling with genetic, biochemical and live-cell imaging data to develop a theoretical model describing and predicting receptor/ligand interactions and endocytotic internalization/trafficking steps more precisely and in a general context.