Kumud R Poudel, Yongming Dong, Hang Yu, Allen Su, Thuong Ho, Yan Liu, Klaus
Schulten, and Jihong Bai.
A time-course of orchestrated endophilin action in sensing, bending,
and stabilizing curved membranes.
Molecular Biology of the Cell, 27:2119-2132, 2016.
(PMC: PMC4927284)
POUD2016
Numerous proteins act in concert to sculpt membrane compartments for cell
signaling and metabolism. These proteins may act as curvature sensors, membrane
benders, and scaffolding molecules. Here, we show that endophilin, a critical
protein for rapid endocytosis, quickly transforms from a curvature sensor to an
active bender upon membrane association. We find that local membrane
deformation does not occur until endophilin inserts its amphipathic helices into lipid
bilayers, supporting an active bending mechanism through wedging. Our time-
course studies show that endophilin continues to drive membrane changes on the
second-to-minute timescale, indicating that the time duration of endocytosis events
constrains the mode of endophilin action. Finally, we reveal a requirement of
coordinated activities between wedging and scaffolding for endophilin to produce
stable membrane tubules in vitro, and to promote synaptic activity in vivo. Together,
these data demonstrate that endophilin is a multi-faceted molecule that precisely
integrates activities of sensing, bending, and stabilizing curvature to sculpt
membranes with speed.
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