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将部分细胞表面内化以去除质膜蛋白以控制细胞信号传递、增殖、分化、存活和迁移等多种生物学过程的重要过程。在受体介导的内吞作用中，受体/配体复合体通常被迅速内化，并通过早期和/或晚期的内吞体递送到最终的靶区。尽管对参与这一基本细胞过程的单个成分进行了深入的研究，但导致受体介导的内吞作用和细胞内货物运输的潜在动力学原理仍然知之甚少。本项目旨在通过将实验数据与理论建模相结合来研究细胞H/KDEL受体Erd2p及其病毒A/B毒素配体在酵母和哺乳动物细胞中的肌动蛋白依赖受体内吞作用和细胞内转运，从而解决这些根本上重要且密切相关的过程。一个主要目标是将数学建模与遗传、生化和活细胞成像数据相结合，以开发一个理论模型，更准确和普遍地描述和预测受体/配体相互作用和内吞内化/转运步骤。

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.