Membrane-elasticity model of Coatless vesicle budding induced by ESCRT complexes.

Bartosz Różycki,Gerhard Hummer,James H Hurley,Evzen Boura,Vijay S Pande

doi:10.1371/journal.pcbi.1002736

Abstract

The formation of vesicles is essential for many biological processes, in particular for the trafficking of membrane proteins within cells. The Endosomal Sorting Complex Required for Transport (ESCRT) directs membrane budding away from the cytosol. Unlike other vesicle formation pathways, the ESCRT-mediated budding occurs without a protein coat. Here, we propose a minimal model of ESCRT-induced vesicle budding. Our model is based on recent experimental observations from direct fluorescence microscopy imaging that show ESCRT proteins colocalized only in the neck region of membrane buds. The model, cast in the framework of membrane elasticity theory, reproduces the experimentally observed vesicle morphologies with physically meaningful parameters. In this parameter range, the minimum energy configurations of the membrane are coatless buds with ESCRTs localized in the bud neck, consistent with experiment. The minimum energy configurations agree with those seen in the fluorescence images, with respect to both bud shapes and ESCRT protein localization. On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process. The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo. Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.

Highlights

Lipid membranes enclose the cytosol of biological cells and compartmentalize their interior
As the assembly matures with the incorporation of Endosomal Sorting Complex Required for Transport (ESCRT)-III, the bud neck is cleaved from the cytosolic side, leaving ESCRTs in the cytosol and the detached spherical intralumenal vesicles (ILVs) in the lumen of the endosome
We identify energetically and kinetically feasible budding pathways, and propose a three-stage mechanism of ESCRT-driven budding: (i) membrane-bound ESCRT-I-II complexes form clusters, or domains, and induce a line tension on the domain boundaries through local segregation of lipids; (ii) as the domain boundary energy exceeds a threshold level, the membrane patch sequestered by the ESCRT assemblies buckles and forms a bud; (iii) the ESCRT-I-II complexes scaffold the bud neck and stabilize a neck diameter optimized for ESCRT-III protein binding and bud scission

Summary

Introduction

Lipid membranes enclose the cytosol of biological cells and compartmentalize their interior. In the degradative transport of membrane proteins from endosomes to lysosomes (Fig. 1), small patches of the endosomal membrane bud into the interior (lumen) of the endosome and detach, forming intralumenal vesicles (ILVs) [6,7] This pathway is catalyzed by the cytosolic Endosomal Sorting Complex Required for Transport (ESCRT) [8,9,10]. As the assembly matures with the incorporation of ESCRT-III, the bud neck is cleaved from the cytosolic side, leaving ESCRTs in the cytosol and the detached spherical ILVs in the lumen of the endosome Because this process involves no protein coat, the shape and energy of the mature buds must be governed primarily by membrane mechanical properties

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Results

Discussion

Conclusion