The ubiquitin-proteasome system and endocytosis

Internalization of membrane proteins has been studied for more than three decades without solving all the underlying mechanisms. Our knowledge of clathrin-mediated endocytosis is certainly sufficient to understand the basic principles. However, more detailed insight is required to recognize why different proteins enter clathrin-coated pits with different rates and affinities. In addition to clathrin coat components, at least two adaptor systems and even more accessory proteins have been described to preselect membrane proteins before they can enter cells. Recent experimental data have identified the ubiquitin-proteasome system as a regulatory system for endocytosis. This system is well-known for its basic regulatory function in protein degradation, and controls a magnitude of key events. The ubiquitin-proteasome system is now identified as a regulator of the endocytosis of selected membrane proteins. In this review we will discuss the complexity and implications of this mechanism for receptor-mediated endocytosis.