SnapShot: Endocytic Trafficking

Abstract

. During this process, cargo mol-ecules are clustered and concentrated within the emerging coated pit. After coat assembly and membrane invagination, which is facilitated by BAR domain-containing proteins, vesicle fission is catalyzed by the recruitment and helical assembly of the GTPase dynamin at the neck of the burgeoning vesicle. Membrane scission requires the cooperative activity of dynamin with SH3 domain-containing proteins, many of which possess BAR domains and regulate the actin cytoskeleton. Actin is required for endocytosis in yeast and may have a regulatory role in mammalian cells. The actin-associated motor proteins myosin 1E and myosin VI are linked to the endocytic machinery via dynamin or synaptojanin and Dab2, respectively. During vesicle uncoating, primary endocytic vesicles may acquire Rab5, a small GTPase involved in transport to early endosomes and in early endosome docking and fusion. Primary endocytic vesicles are targeted to and fuse with early endosomes expressing phosphatidylinositol(3)-phosphate, PI(3)P, in a process dependent on Rab5 effector proteins and early endosomal SNAREs. Differential sorting of cargo destined for recycling (requiring Rab11 and possibly Rab4) or for late endosome/lysosomal degradation (requiring Rab7) can occur at the level of clathrin-coated pits and be com-pleted in early endosomal subdomains. Transport of cargo from early endosomes to the trans-Golgi network requires the retromer protein complex.