Mechanics of dynamin-mediated membrane fission - PubMed (original) (raw)

Review

Mechanics of dynamin-mediated membrane fission

Sandrine Morlot et al. Annu Rev Biophys. 2013.

Abstract

In eukaryotic cells, membrane compartments are split into two by membrane fission. This ensures discontinuity of membrane containers and thus proper compartmentalization. The first proteic machinery implicated in catalyzing membrane fission was dynamin. Dynamin forms helical collars at the neck of endocytic buds. This structural feature suggested that the helix of dynamin could constrict in order to promote fission of the enclosed membrane. However, verifying this hypothesis revealed itself to be a challenge, which inspired many in vitro and in vivo studies. The primary goal of this review is to discuss recent structural and physical data from biophysical studies that have refined our understanding of the dynamin mechanism. In addition to the constriction hypothesis, other models have been proposed to explain how dynamin induces membrane fission. We present experimental data supporting these various models and assess which model is the most probable.

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Figures

Figure 1

Figure 1

Dynamin assembly. (a) Schematic representations of dynamin helix in four different conditions: in solution, on membrane templates, on membrane templates with BAR domains, and in vivo. The helical diameter is identical in all conditions in the absence of GTP. However, the pitch is longer in the presence of BAR domains and in vivo. (b) Crystal (top) and schematic (bottom) structures of a dynamin dimer (PDB ID: 3SHN). The proline-rich domain (PRD) is not represented. Monomers interact in a cross shape via their stalk. (c) Schematic representations of a dynamin helix around a lipid tube ( gray). Radial (right) and transverse (left) views show how dimers assemble into a helix. Abbreviation: BSE, bundling signal element.

Figure 2

Figure 2

Force-generating cycles for myosin and dynamin. (a) Actomyosin ATPase cycle. Upon ATP binding the myosin head (red ) detaches from the actin filament ( gray). After ATP hydrolysis myosin rebinds to actin. Release of ADP triggers the powerstroke: mechanical motion of the lever arm. (b) Putative dynamin GTPase cycle. In the case of dynamin, the powerstroke occurs during GTP hydrolysis. According to structural data, conformational changes are observed between the GMP-PCP-bound state and the GDP AIF4−-bound state. Thus, GDP release could be linked to dissociation of the G domain from its substrate, · i.e., the opposite G domain in the consecutive turn. GTP binding could then reactivate the G domain interactions. (c) GTPase cycles for two consecutive rows of four dimers. After each monomer completes GTP hydrolysis, the two adjacent turns have walked on each other, thus constricting the lipid tube. Note that GTPase cycles are not synchronized. Here cycles of the eight dimers are represented concomitantly for clarity.

Figure 3

Figure 3

Constriction model. Membrane fission occurs in two steps. In the first step, the dynamin helix constricts the lipid nanotube so that its radius decreases. This step is controlled by the concentration of GTP, as GTP is the energy source of dynamin, and the torque subsequently delivered. In the second step, the constricted tube spontaneously hemifuses and breaks. The kinetics of this step depends on membrane elasticity.

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