Table 1. Mechanisms of clathrin-independent endocytosis*.
Characteristics | Caveolar‡ | RhoA-regulated | CDC42-regulated | ARF6-regulated |
---|---|---|---|---|
Cargo§ | Modified albumins | IL-2R-β | GPI-AP¶ | MHC I |
GSL analogues | IL-2R-αβ | Fluid-phase markers | β1 integrin | |
SV40; EV1 | γc-cytokine receptor‖ | CtxB¶ | E-cadherin | |
Some integrins (for example, β1) | IgE receptor‖ | VacA toxin | GPI-AP | |
CtxB¶ | Aerolysin | CPE | ||
Ab-clustered GPI-AP# | IL-2R-α (Tac) | |||
Structural components and machinery associated with pathway |
CAV1 | RhoA | CDC42 | ARF6 |
PV1 | Dynamin | Flotillin-1** | Flotillin-1** | |
Src | RAB5 | RAB11 | ||
PKC-α | PI3K | RAB22 | ||
Dynamin | EEA1 | PI3K | ||
RAB5 | ||||
Primary carriers | 50–80 nm diameter caveolin-coated vesicles and ‘grape-like’ aggregates | Uncoated vesicles | Clathrin- and dynamin-independent carriers (CLICs) | Unknown |
Identity of earliest acceptor compartment | Caveosome or early endosome | Early endosome | GPI-AP enriched early endosomal compartments (GEECs) | Early tubular recycling compartment |
Ab, antibody; ARF6, ADP-ribosylation factor-6; CAV1, caveolin-1; CPE, carboxypeptidase E; CtxB, cholera toxin B; EEA1, early endosomal antigen-1; EV1, Echo virus; GPI-AP, glycosyl phosphatidylinositol-anchored protein; GSL, glycosphingolipid; IgE, immunoglobulin E; IL-2R, interleukin-2 receptor; MHC I, major histocompatibility complex I; PI3K, phosphatidylinositol 3-kinase; PKC-α, protein kinase C-α; PV1, Polio virus; SV40, simian virus-40; VacA, Helicobacter pylori vacuolating toxin.
See Supplementary information S1 (table) for inhibitors and dominant negative proteins that are used to distinguish among the various clathrin-independent mechanisms.
The best caveolar markers vary with cell type (see text).
See text for representative references for different cargo molecules.
Although the specific requirements for endocytosis of molecules via a given pathway have not been rigorously established, available evidence suggests this classification.
Originally described as a caveolar marker, but recent data suggests uptake by the CDC42-regulated pathway31,33,104.
Crosslinking of GPI-APs shifts internalization from the CDC42-dependent pathway to the caveolar pathway37,105,106.
Currently, it is not clear if flotillin-1 is part of one or both of these pathways (see text).