Endocytic accessory factors and regulation of clathrin-mediated endocytosis

Abstract

Up to 60 different proteins are recruited to the site of clathrin-mediated endocytosis in an ordered sequence. These accessory proteins have roles during all the different stages of clathrin-mediated endocytosis. First, they participate in the initiation of the endocytic event, thereby determining when and where endocytic vesicles are made; later they are involved in the maturation of the clathrin coat, recruitment of specific cargo molecules, bending of the membrane, and finally in scission and uncoating of the nascent vesicle. In addition, many of the accessory components are involved in regulating and coupling the actin cytoskeleton to the endocytic membrane. We will discuss the different accessory components and their various roles. Most of the data comes from studies performed with cultured mammalian cells or yeast cells. The process of endocytosis is well conserved between these different organisms, but there are also many interesting differences that may shed light on the mechanistic principles of endocytosis.

Figure 1.

Clathrin-mediated endocytosis in mammalian and yeast cells. The basic sequence of events is similar but the requirements for clathrin, actin, and dynamin differ between these organisms. The shape of the endocytic intermediates is approximately spherical in mammals, but tubular in yeast.

Figure 2.

Different mechanisms of membrane bending. (A) Local clustering of lipids with large head groups. (B) Insertion of an amphipathic helix or a loop into the membrane. (C) Binding of pre-curved proteins to the membrane surface. (D) Crowding of membrane-associated proteins.