Analysis of the function of Lamellipodin in receptor-mediated endocytosis

人体是由数百万个细胞组成的。为了使身体正常运作，这些细胞必须相互沟通。它们通过发出信号进行交流，这些信号可以通过激活细胞表面的受体被其他细胞识别。反过来，这些被激活的受体刺激细胞做出反应并改变它们的行为。信号通过被小泡吸收而从细胞表面移除激活的受体而停止。这个过程被称为“内吞作用”。内吞作用对我们身体的正常功能很重要，但如果它“出错”，就会导致疾病。例如，在许多癌症的情况下，激活的受体可能不会被有效地吸收，因此这些受体的刺激可能会增加，导致细胞不受控制地生长。我们拟利用实验室培养的单细胞研究生长因子受体内吞作用的基本机制。我们将分析细胞通常如何使用生化方法控制受体的摄取。我们还将通过荧光染料标记单个蛋白质，使它们被招募到囊泡中。这将使我们能够使用显微镜实时分析活细胞中的招募。我们的研究可能使我们能够揭示不同蛋白质对受体摄取的作用。该项目的结果将对我们体内单个细胞的正常功能提供新的见解，从长远来看，可能为开发针对受体信号改变的疾病（如癌症）的靶向治疗提供知识。

The human body is composed of millions of cells. In order for the body to function properly these cells have to communicate with each other. They communicate by sending out signals that can be recognized by other cells through the activation of receptors on their cell surface. In turn, these activated receptors stimulate cells to react and change their behavior. The signal is stopped by removal of the activated receptors from the cell surface by uptake into small vesicles. This process is called 'endocytosis'. Endocytosis is important for the normal functioning of our body but if it 'goes wrong' it can lead to disease. For example, in the case of many cancers activated receptors might not be taken up efficiently and hence stimulation from these receptors might increase causing cells to grow uncontrolled. We propose to study the basic mechanisms of endocytosis of growth factor receptors using single cells cultured in the laboratory. We will analyze how cells normally control the uptake of receptors using biochemical approaches. We will also visualize individual proteins recruited to the vesicles by labeling them with a fluorescent dye. This will allow us to analyze the recruitment in living cells in real time using a microscope. Our study might permit us to uncover the role of the different proteins for the uptake of the receptors. The outcome of the project will give novel insights into the normal function of individual cells within our body and in the long run may provide the knowledge for the development of targeted therapies for diseases with altered receptor signaling such as cancer.