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Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit.

Cocucci E, Gaudin R, Kirchhausen T - Mol. Biol. Cell (2014)

Bottom Line: The first is associated with coated pit maturation; the second, with fission of the membrane neck of a coated pit.A large fraction of budding coated pits recruit between 26 and 40 dynamins (between 1 and 1.5 helical turns of a dynamin collar) during the recruitment phase associated with neck fission; 26 are enough for coated vesicle release in cells partially depleted of dynamin by RNA interference.We discuss how these results restrict models for the mechanism of dynamin-mediated membrane scission.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, and Cellular and Molecular Medicine Program, Boston Children's Hospital, Boston, MA 02115 Department of Pediatrics, Harvard Medical School, Boston, MA 02115.

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Proposed models for dynamin-mediated scission. (A) Isotropic contraction model requiring close to two turns of the basic helix. Consecutive cycles of GTPase activation between domains phasing opposing rungs provide the power stroke that ultimately compresses the spiral to reach conditions of membrane hemifission and eventual membrane scission. (Adapted from Faelber et al., 2011.) (B) Circumferential twist model proposed in this study, in which two dimers at the leading edge of a dynamin rung interact through their opposing GTPase domains (yellow). Activation of the GTPase activity induces a local conformational change—in effect, a power stroke that locally tightens the approaching ends of the assembled rung. To this effect, arrival of a dynamin dimer (green) to one of the rung ends (yellow) results in the GTPase activation and conformational change of the opposing domains (green and red) associated with the next power stroke. A limited number of such sequential additions would be sufficient to tighten the rung, eventually leading to membrane hemifission and membrane scission.
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Figure 10: Proposed models for dynamin-mediated scission. (A) Isotropic contraction model requiring close to two turns of the basic helix. Consecutive cycles of GTPase activation between domains phasing opposing rungs provide the power stroke that ultimately compresses the spiral to reach conditions of membrane hemifission and eventual membrane scission. (Adapted from Faelber et al., 2011.) (B) Circumferential twist model proposed in this study, in which two dimers at the leading edge of a dynamin rung interact through their opposing GTPase domains (yellow). Activation of the GTPase activity induces a local conformational change—in effect, a power stroke that locally tightens the approaching ends of the assembled rung. To this effect, arrival of a dynamin dimer (green) to one of the rung ends (yellow) results in the GTPase activation and conformational change of the opposing domains (green and red) associated with the next power stroke. A limited number of such sequential additions would be sufficient to tighten the rung, eventually leading to membrane hemifission and membrane scission.

Mentions: The radius of the membrane tubule within a GMPPCP dynamin sheath is ∼5 nm (from the axis to the center of the bilayer; Chappie et al., 2011). Spontaneous hemifission is believed to require a radius of ∼3 nm (Kozlovsky and Kozlov, 2003). Conformational changes in a dynamin collar could produce such a contraction either by a rotation of the stalks toward a more radial orientation, forcing the PH domains inward while leaving the helical parameters of the outer layer more or less unchanged, or by a decrease in the number of dynamins per turn of the helix, reducing both its outer and inner diameter without changing the radial disposition of the stalks. These two alternatives correspond roughly to the models proposed by Chappie et al. (2011) and by Smirnova et al. (1999) and Faelber et al. (2011). The former is, in its simplest form, an isotropic squeeze (Figure 10A); the latter, a circumferential twist (Figure 10B and Supplemental Movies S1–S3). The isotropic contraction model requires nearly a full turn of paired GTPase domains—that is, nearly two turns of the basic helix. The circumferential twist model requires simply that the assembly reach a state in which one or more pairs of GTPase domains interact. Our data appear to favor the latter picture.


Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit.

Cocucci E, Gaudin R, Kirchhausen T - Mol. Biol. Cell (2014)

Proposed models for dynamin-mediated scission. (A) Isotropic contraction model requiring close to two turns of the basic helix. Consecutive cycles of GTPase activation between domains phasing opposing rungs provide the power stroke that ultimately compresses the spiral to reach conditions of membrane hemifission and eventual membrane scission. (Adapted from Faelber et al., 2011.) (B) Circumferential twist model proposed in this study, in which two dimers at the leading edge of a dynamin rung interact through their opposing GTPase domains (yellow). Activation of the GTPase activity induces a local conformational change—in effect, a power stroke that locally tightens the approaching ends of the assembled rung. To this effect, arrival of a dynamin dimer (green) to one of the rung ends (yellow) results in the GTPase activation and conformational change of the opposing domains (green and red) associated with the next power stroke. A limited number of such sequential additions would be sufficient to tighten the rung, eventually leading to membrane hemifission and membrane scission.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 10: Proposed models for dynamin-mediated scission. (A) Isotropic contraction model requiring close to two turns of the basic helix. Consecutive cycles of GTPase activation between domains phasing opposing rungs provide the power stroke that ultimately compresses the spiral to reach conditions of membrane hemifission and eventual membrane scission. (Adapted from Faelber et al., 2011.) (B) Circumferential twist model proposed in this study, in which two dimers at the leading edge of a dynamin rung interact through their opposing GTPase domains (yellow). Activation of the GTPase activity induces a local conformational change—in effect, a power stroke that locally tightens the approaching ends of the assembled rung. To this effect, arrival of a dynamin dimer (green) to one of the rung ends (yellow) results in the GTPase activation and conformational change of the opposing domains (green and red) associated with the next power stroke. A limited number of such sequential additions would be sufficient to tighten the rung, eventually leading to membrane hemifission and membrane scission.
Mentions: The radius of the membrane tubule within a GMPPCP dynamin sheath is ∼5 nm (from the axis to the center of the bilayer; Chappie et al., 2011). Spontaneous hemifission is believed to require a radius of ∼3 nm (Kozlovsky and Kozlov, 2003). Conformational changes in a dynamin collar could produce such a contraction either by a rotation of the stalks toward a more radial orientation, forcing the PH domains inward while leaving the helical parameters of the outer layer more or less unchanged, or by a decrease in the number of dynamins per turn of the helix, reducing both its outer and inner diameter without changing the radial disposition of the stalks. These two alternatives correspond roughly to the models proposed by Chappie et al. (2011) and by Smirnova et al. (1999) and Faelber et al. (2011). The former is, in its simplest form, an isotropic squeeze (Figure 10A); the latter, a circumferential twist (Figure 10B and Supplemental Movies S1–S3). The isotropic contraction model requires nearly a full turn of paired GTPase domains—that is, nearly two turns of the basic helix. The circumferential twist model requires simply that the assembly reach a state in which one or more pairs of GTPase domains interact. Our data appear to favor the latter picture.

Bottom Line: The first is associated with coated pit maturation; the second, with fission of the membrane neck of a coated pit.A large fraction of budding coated pits recruit between 26 and 40 dynamins (between 1 and 1.5 helical turns of a dynamin collar) during the recruitment phase associated with neck fission; 26 are enough for coated vesicle release in cells partially depleted of dynamin by RNA interference.We discuss how these results restrict models for the mechanism of dynamin-mediated membrane scission.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, and Cellular and Molecular Medicine Program, Boston Children's Hospital, Boston, MA 02115 Department of Pediatrics, Harvard Medical School, Boston, MA 02115.

Show MeSH
Related in: MedlinePlus