Role of curvature sensing/inducing BAR domain proteins in clathrin-independent endocytosis

Abstract

Endocytosis is an essential cellular process required for uptake of nutrients from cell environment and turnover of plasma membrane components. Clathrin-mediated endocytosis is by far the best characterized endocytic process. Since the mid-90's, the existence of endocytic routes independent of clathrin emerged. Therefore, the most challenging question in membrane biology rose: how could the plasma membrane be deformed in the absence of an organized clathrin coat? Until today, this process is not fully understood. First attempts to shed light into this topic demonstrated the requirement of glycosphingolipids for membrane deformation in lectin-driven endocytosis. Recently, BAR domain proteins (BAR stands for Bin/Amphiphysin/Rvs) have been described to be crucial for clathrin-independent endocytic routes. BAR domain proteins interact with membranes and act as curvature sensors/inducers. The function of BAR domain proteins remains unclear in the landscape of clathrin-independent endocytosis, and especially the endocytic pit formation. We hypothesize that this protein family constitute a module, which defines cargo specificity and is able to deform plasma membrane in clathrin-independent endocytic processes. To verify this hypothesis, we will perform a knock-down screen of various BAR domain proteins in mammalian cells and analyse the abundance of plasma membrane proteins via quantitative proteomics. Identified BAR domain proteins/potential plasma membrane cargoes couples will be selected, and deeply characterized using advanced cell biology techniques and model membranes: Do they constitute new clathrin-independent endocytic routes? What is the function of the BAR domain proteins in the new endocytic processesses