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. Author manuscript; available in PMC: 2024 Dec 10.
Published in final edited form as: Nat Rev Mol Cell Biol. 2007 Aug 1;8(8):603–12. doi: 10.1038/nrm2216

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).