Abstract
SummaryMembrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis. We call this mechanism friction-driven scission (FDS). In cells, motors pull tubes, particularly during endocytosis. Through reconstitution, we show that motors not only can pull out and extend protein-scaffolded tubes but also can cut them by FDS. FDS is generic, operating even in the absence of amphipathic helices in the BAR domain, and could in principle apply to any high-friction protein and membrane assembly.
Highlights
Endocytosis allows cells to internalize nutrients and proteins and is used by pathogens in the course of infection (McMahon and Boucrot, 2011)
In clathrin-mediated endocytosis (CME) in mammalian cells, scission requires the assembly of dynamin at the neck of the vesicle, and it can be assisted by actin polymerization (Boulant et al, 2011; Ferguson et al, 2009) and Bin/Amphiphysin/Rvs (BAR) proteins (Meinecke et al, 2013; Neumann and Schmid, 2013; Sundborger et al, 2011; Yoshida et al, 2004)
We considered two BAR proteins: endophilin A2 (endoA2), containing four amphipathic helices (AHs) per dimer, and b2 centaurin, containing no AHs
Summary
Endocytosis allows cells to internalize nutrients and proteins and is used by pathogens in the course of infection (McMahon and Boucrot, 2011). In CIE, which typically involves tubular membrane structures, scission appears to require a more equal division of labor among these three proteins (Renard et al, 2015). In both CME and CIE, several scission modules may coexist in a single endocytic pathway, rendering the process more robust yet obscuring the underlying mechanisms. Line tension at the edge of lipid domains can generate enough constriction to drive spontaneous vesiculation or scission of tubes (Allain et al, 2004; Romer et al, 2010) In yeast, it may be assisted by forces exerted by actin polymerization (Liu et al, 2006). Shallow insertion of amphipathic helices (AHs) into the bilayer may lead to scission of small vesicles, as observed in the case of epsin and N-BAR proteins (Boucrot et al, 2012; Simunovic et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
