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Review
. 2009 Sep 4;325(5945):1217-20.
doi: 10.1126/science.1171004.

Conserved functions of membrane active GTPases in coated vesicle formation

Affiliations
Review

Conserved functions of membrane active GTPases in coated vesicle formation

Thomas J Pucadyil et al. Science. .

Abstract

Coated vesicles concentrate and package cargo molecules to mediate their efficient transport between intracellular compartments. Cytosolic coat proteins such as clathrin and adaptor complexes and coat protein complex I (COPI) and COPII self-assemble to deform the membrane and interact directly with cargo molecules to capture them in nascent buds. The guanosine triphosphatases (GTPases) Arf, Sar1, and dynamin are core components of the coated vesicle machinery. These GTPases, which associate with and dissociate from donor membranes in a guanosine triphosphate-dependent manner, can also actively remodel membranes. Recent evidence suggests that, although structurally diverse, Arf family GTPases and dynamin may play mechanistically similar roles as fidelity monitors that govern cargo packaging and coated vesicle maturation and as components of the fission machinery to mediate vesicle release.

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Figures

Fig. 1
Fig. 1
General scheme of coated vesicle formation. This process involves the initial assembly of coat subunits on the membrane, during which cargo recognition and sorting takes place, followed by maturation, during which the coat and underlying membrane acquires curvature. Scission of the coated bud finally generates a coated vesicle. The reported involvement of the membrane active GTPases, Arf1, Sar1 and dynamin, during each of these stages is described.
Fig. 2
Fig. 2
Membrane active GTPases in coated vesicular transport. (A) Structure of myristoylated Arf1 in the GDP-bound state (PDB 2K5U) (51). The myristoyl chain and the first 16 residues are shown in green. (B) Structure of Arf1 in the GTP-bound state (PDB 1O3Y) (52). Gly16 and a schematic representation of the exposed N-terminal helix without the myristoyl chain (dotted circle) are shown in green. (C) Membrane tubules formed by GTP-bound Arf1 (20). (D) Structure of GDP-bound Sar1 (PDB 2GAO). Residues 13–26 are shown in green. (E) Structure of GTP-bound Sar1 (PDB 1M2O) (53). Gly24 and a representation of the extended N-terminal helix (dotted circle) are shown in green. (F) Membrane tubules formed by GTP-bound Sar1 (24). (G) Structure of dynamin1 PH domain (PDB 1DYN) (54). The variable loops VL1 (green), VL2 (red) and VL3 (gold) are highlighted. (H) Membrane tubules formed by dynamin1 (34).
Fig. 3
Fig. 3
General model for scission of coated-buds. We propose that the restricted localization of membrane active GTPases to the necks of budding coated vesicles could catalyze membrane fission. In the case of clathrin-coated buds (A), dynamin is localized at the neck where multiple cycles of membrane association, spontaneous self-assembly, GTP hydrolysis to produce the GDP-bound state, and membrane dissociation leads to scission. The donor membrane-localized GEF activity and coat-localized GAP activity could restrict Arf1 and Sar1 localization to the necks of COPI- and COPII-coated buds (B). As a consequence, reversible membrane association of these GTPases at the neck could eventually lead to scission of the coated-bud.

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