Constraints and frustration in the clathrin-dependent endocytosis pathway

Clathrin-dependent endocytosis is the major pathway for the entry of most surface receptors and their ligands. It is controlled by clathrin-coated structures that are endowed with the ability to cluster receptors and locally bend the plasma membrane, leading to the formation of receptorcontaining vesicles budding into the cytoplasm. This canonical role of clathrin-coated structures has been repeatedly demonstrated to play a fundamental role in a wide range of aspects of cell physiology. However, it is now clearly established that the ability of clathrin-coated structures to bend the membrane can be disrupted. In addition to chemical or genetic alterations, many environmental conditions can physically prevent or slow membrane deformation and/or budding of clathrin-coated structures. The resulting frustrated endocytosis is not only a passive consequence but serves very specific and important cellular functions. Here we provide a historical perspective as well as a definition of frustrated endocytosis in the clathrin pathway before describing its causes and many functional consequences.