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PhD Student, UCL

PINBOARD SUMMARY

Endocytic pathways regulate the uptake of extracellular micronutrients and turnover of plasma membrane components, thus acting as key mediators between the cell and its external environment. The fast endophilin-mediated endocytosis (FEME) pathway is a recently characterised clathrin-independent endocytic route notable for its speed and reliance on receptor-ligand interaction for activation. Active in a range of cell types, the pathway is known to be hijacked by bacterial toxins and is important in signalling and cell motility. Incomplete knowledge of the receptors which trigger FEME uptake limits understanding of the pathway’s functional roles. Thus far, a small number of receptors have been verified as FEME cargoes including G-protein coupled receptors, receptor tyrosine kinases and the cytokine receptor IL-2R. Our work aims to expand the repertoire of known FEME cargoes in order to further illuminate the pathway's physiological roles.

3 ITEMS PINNED

Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis.

Abstract: During endocytosis, energy is invested to narrow the necks of cargo-containing plasma membrane invaginations to radii at which the opposing segments spontaneously coalesce, thereby leading to the detachment by scission of endocytic uptake carriers. In the clathrin pathway, dynamin uses mechanical energy from GTP hydrolysis to this effect, assisted by the BIN/amphiphysin/Rvs (BAR) domain-containing protein endophilin. Clathrin-independent endocytic events are often less reliant on dynamin, and whether in these cases BAR domain proteins such as endophilin contribute to scission has remained unexplored. Here we show, in human and other mammalian cell lines, that endophilin-A2 (endoA2) specifically and functionally associates with very early uptake structures that are induced by the bacterial Shiga and cholera toxins, which are both clathrin-independent endocytic cargoes. In controlled in vitro systems, endoA2 reshapes membranes before scission. Furthermore, we demonstrate that endoA2, dynamin and actin contribute in parallel to the scission of Shiga-toxin-induced tubules. Our results establish a novel function of endoA2 in clathrin-independent endocytosis. They document that distinct scission factors operate in an additive manner, and predict that specificity within a given uptake process arises from defined combinations of universal modules. Our findings highlight a previously unnoticed link between membrane scaffolding by endoA2 and pulling-force-driven dynamic scission.

Pub.: 18 Dec '14, Pinned: 04 Jul '17