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

Różycki B, Boura E, Hurley JH, Hummer G - PLoS Comput. Biol. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

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.

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ESCRT protein assemblies (blue) facilitate the sorting of ubiquitinated membrane proteins (green) and formation of intralumenal vesicles (ILV).The ESCRT proteins assemble on the membrane side opposite the vesicle bud (C) and do not enter the ILV lumen for possible recycling (D). Energy input from ATP hydrolysis accelerates disassembly of the ESCRT machinery (D), but is not required in steps (A–C).
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pcbi-1002736-g001: ESCRT protein assemblies (blue) facilitate the sorting of ubiquitinated membrane proteins (green) and formation of intralumenal vesicles (ILV).The ESCRT proteins assemble on the membrane side opposite the vesicle bud (C) and do not enter the ILV lumen for possible recycling (D). Energy input from ATP hydrolysis accelerates disassembly of the ESCRT machinery (D), but is not required in steps (A–C).

Mentions: Lipid membranes enclose the cytosol of biological cells and compartmentalize their interior. The structure and contents of cellular membranes are actively controlled to sustain the vital functions of the cell. Transport vesicles are used to traffic membrane-bound proteins between cellular compartments. The best-characterized pathways of vesicle formation include those facilitated by BAR domain proteins [1] and by the coat protein clathrin with its adaptors [2]. Coat proteins impose their curved shape onto the membrane, thereby promoting vesicle curvature in an intuitively straightforward and computationally well-characterized process [3]–[5]. 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]–[10]. The ESCRT proteins are not internalized in ILVs, but rather recycled continuously in the cytosol [11], [12]. To avoid the consumption of ESCRT proteins within the ILVs, these vesicles contain no protein coat to template their shape. Rather, these vesicles are initially formed as buds whose necks are stabilized by an assembly of ESCRT-I and -II [13]. 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.


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

Różycki B, Boura E, Hurley JH, Hummer G - PLoS Comput. Biol. (2012)

ESCRT protein assemblies (blue) facilitate the sorting of ubiquitinated membrane proteins (green) and formation of intralumenal vesicles (ILV).The ESCRT proteins assemble on the membrane side opposite the vesicle bud (C) and do not enter the ILV lumen for possible recycling (D). Energy input from ATP hydrolysis accelerates disassembly of the ESCRT machinery (D), but is not required in steps (A–C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475702&req=5

pcbi-1002736-g001: ESCRT protein assemblies (blue) facilitate the sorting of ubiquitinated membrane proteins (green) and formation of intralumenal vesicles (ILV).The ESCRT proteins assemble on the membrane side opposite the vesicle bud (C) and do not enter the ILV lumen for possible recycling (D). Energy input from ATP hydrolysis accelerates disassembly of the ESCRT machinery (D), but is not required in steps (A–C).
Mentions: Lipid membranes enclose the cytosol of biological cells and compartmentalize their interior. The structure and contents of cellular membranes are actively controlled to sustain the vital functions of the cell. Transport vesicles are used to traffic membrane-bound proteins between cellular compartments. The best-characterized pathways of vesicle formation include those facilitated by BAR domain proteins [1] and by the coat protein clathrin with its adaptors [2]. Coat proteins impose their curved shape onto the membrane, thereby promoting vesicle curvature in an intuitively straightforward and computationally well-characterized process [3]–[5]. 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]–[10]. The ESCRT proteins are not internalized in ILVs, but rather recycled continuously in the cytosol [11], [12]. To avoid the consumption of ESCRT proteins within the ILVs, these vesicles contain no protein coat to template their shape. Rather, these vesicles are initially formed as buds whose necks are stabilized by an assembly of ESCRT-I and -II [13]. 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.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

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.

Show MeSH
Related in: MedlinePlus