Fast and ultrafast endocytosis

- Reaction to stress, chemotaxis or synaptic vesicle exocytosis requires fast endocytosis.
- Clathrin-mediated endocytosis may be too slow to regulate fast physiological responses.
- Several fast clathrin-independent endocytic processes have been identified.
- Ultrafast endocytosis mediates rapid membrane removal at synapses.
- Fast-endophilin-mediated endocytosis (FEME) is triggered upon receptor activation.

Clathrin-mediated endocytosis (CME) is the main endocytic pathway supporting housekeeping functions in cells. However, CME may be too slow to internalize proteins from the cell surface during certain physiological processes such as reaction to stress hormones ('fight-or-flight' reaction), chemotaxis or compensatory endocytosis following exocytosis of synaptic vesicles or hormone-containing vesicles. These processes take place on a millisecond to second timescale and thus require very rapid cellular reaction to prevent overstimulation or exhaustion of the response. There are several fast endocytic processes identified so far: macropinocytosis, activity-dependent bulk endocytosis (ABDE), fast-endophilin-mediated endocytosis (FEME), kiss-and-run and ultrafast endocytosis. All are clathrin-independent and are not constitutively active but may use different molecular mechanisms to rapidly remove receptors and proteins from the cell surface. Here, we review our current understanding of fast and ultrafast endocytosis, their functions, and molecular mechanisms.