The endocytosis machinery

Alexander Sorkin

Dept of Pharmacology, University of Colorado Health Science Center, 4200 E. 9th Ave, Denver, CO 80262, USA

In mammalian cells, cargo can be endocytosed via clathrin-coated pits, the clathrin-independent pathway or caveolae. In yeast cells the morphology of the internalization step is not yet defined. All internalization pathways lead to the appearance of cargo in the peripheral early endosomes. Coated vesicles must be at least partially uncoated to fuse with early endosomes. Early endosomes then undergo homotypic fusion. From early endosomes cargo is recycled back to the plasma membrane, sorted to the late recycling compartment or delivered to late endosomes (the prelysosomal compartment or prevacuole) by means of carrier vesicles or through a ‘maturation’ process (a change in biochemical composition and morphology). Carrier vesicles and late endosomes often display a morphology typical of multi-vesicular bodies, which contain internal membrane structures. These structures appear to be formed by invagination of the endosomal membrane. Late endosomes either mature into lysosomes or transfer cargo to lysosomes through vesicular intermediates. The recycling compartment is responsible for delivery of the cargo back to the cell surface. The endosome/lysosome system can send to and receive cargo from the trans-Golgi network (TGN) via vesicular intermediates. Routes of internalization and intracellular trafficking are shown by black arrows and labelled in black.

The figure shows the major proteins involved in regulation of endocytic pathways. Mammalian proteins are in shown in red, and yeast proteins are shown in green. Where the mammalian and yeast protein have the same name, this is given in green (AP-3, Vps17p, 26p, 29p, 35p) or red (GGAs). Organelles are labelled in blue, with the exception of yeast-specific names, which are green. Protein-protein interaction (EH, Eps15 homology, PH, pleckstrin homology; SH3, SRC homology 3) domains are indicated. Closest mammalian and yeast homologs are separated by a solidus (/). Mammalian homologs of yeast proteins involved in the internalization step are actin (Act1p), calmodulin (Cmd1p), type I (unconventional) myosin (Myo5p); EH-containing proteins (Pan1p and End3p), amphyphysins (Rvs161p and Rvs167p), synaptojanin (Sjl1p), and the clathrin heavy and light chains (Chc1p and Clc1p, respectively). Proteins, for which biochemical, functional or genetic interactions have been demonstrated are shown in boxes. Each AP-1, AP-2 and AP-3 complex consists of four subunits: ß, µ and {varsigma} are highly homologous in all three complexes, whereas {gamma}, {alpha} and {delta} are specific for AP-1, AP-2 and AP-3, respectively. ß-arrestin can bind to clathrin and AP-2 and is involved in coated-pit recruitment of G-protein-coupled receptors. Lipids: PPIs, polyphosphoinositides; PtdIns, phosphatidylinositol; PtdIns(3)P, PtdIns 3-phosphate; PtdIns(3,5)P2, PtdIns 3,5-bisphosphate; PtdIns(5)Ps, PtdIns phosphates phosphorylated at position 5; PtdInsPs, PtdIns(5)Ps in which the phosphate has been removed from position 5. Other abbreviations: NSF, N-ethylmaleimide-sensitive factor; v- and t-SNARE, vesicular- and target-membrane soluble NSF attachment protein receptors. Vps, vacuolar protein sorting.

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