Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission


Dynamin, a crucial factor in endocytosis1,2,3, is a member of a family of GTPases that participates in membrane fission4,5,6. It was initially proposed to act as a machine that constricts and cuts the neck of nascent vesicles in a GTP-hydrolysis-dependent reaction4,5, but subsequent studies suggested alternative models2,7,8. Here we monitored the effect of nucleotides on dynamin-coated lipid tubules in real time. Addition of GTP, but not of GDP or GTP-γS, resulted in twisting of the tubules and supercoiling, suggesting a rotatory movement of the helix turns relative to each other during GTP hydrolysis. Rotation was confirmed by the movement of beads attached to the tubules. Twisting activity produced a longitudinal tension that was released by tubule breakage when both ends of the tubule were anchored. Fission also occurred when dynamin and GTP were added to lipid tubules that had been generated from liposomes by the motor activity of kinesin on microtubules. No fission events were observed in the absence of longitudinal tension. These findings demonstrate a mechanoenzyme activity of dynamin in endocytosis, but also imply that constriction is not sufficient for fission. At the short necks of endocytic vesicles, other factors6,9,10 leading to tension may cooperate with the constricting activity of dynamin to induce fission11,12,13.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Generation and growth of dynamin-coated membrane tubules.
Figure 2: Effect of guanylnucleotides on dynamin-coated tubules.
Figure 3: Dynamin-dependent fragmentation of membrane tubules generated from giant liposomes by kinesin on a microtubule network.
Figure 4: Twisting activity of the dynamin coat.


  1. 1

    Koenig, J. H. & Ikeda, K. Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J. Neurosci. 9, 3844–3860 (1989)

    CAS  Article  PubMed  Google Scholar 

  2. 2

    Sever, S., Damke, H. & Schmid, S. L. Garrotes, springs, ratchets, and whips: putting dynamin models to the test. Traffic 1, 385–392 (2000)

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Thompson, H. M. & McNiven, M. A. Dynamin: switch or pinchase? Curr. Biol. 11, R850 (2001)

    CAS  Article  PubMed  Google Scholar 

  4. 4

    Takei, K., McPherson, P. S., Schmid, S. L. & De Camilli, P. Tubular membrane invaginations coated by dynamin rings are induced by GTP-γS in nerve terminals. Nature 374, 186–190 (1995)

    ADS  CAS  Article  PubMed  Google Scholar 

  5. 5

    Hinshaw, J. E. & Schmid, S. L. Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature 374, 190–192 (1995)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Praefcke, G. J. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nature Rev. Mol. Cell Biol. 5, 133–147 (2004)

    CAS  Article  Google Scholar 

  7. 7

    Sever, S., Muhlberg, A. B. & Schmid, S. L. Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis. Nature 398, 481–486 (1999)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Stowell, M. H., Marks, B., Wigge, P. & McMahon, H. T. Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring. Nature Cell Biol. 1, 27–32 (1999)

    CAS  Article  Google Scholar 

  9. 9

    Slepnev, V. I. & De Camilli, P. Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nature Rev. Neurosci. 1, 161–172 (2000)

    CAS  Article  Google Scholar 

  10. 10

    Merrifield, C. J., Perrais, D. & Zenisek, D. Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells. Cell 121, 593–606 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Itoh, T. et al. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev. Cell 9, 791–804 (2005)

    CAS  Article  PubMed  Google Scholar 

  12. 12

    Qualmann, B., Kessels, M. M. & Kelly, R. B. Molecular links between endocytosis and the actin cytoskeleton. J. Cell Biol. 150, F111–F116 (2000)

    CAS  Article  PubMed  Google Scholar 

  13. 13

    Cao, H. et al. Cortactin is a component of clathrin-coated pits and participates in receptor-mediated endocytosis. Mol. Cell. Biol. 23, 2162–2170 (2003)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Sweitzer, S. M. & Hinshaw, J. E. Dynamin undergoes a GTP-dependent conformational change causing vesiculation. Cell 93, 1021–1029 (1998)

    CAS  Article  Google Scholar 

  15. 15

    Takei, K., Slepnev, V. I., Haucke, V. & De Camilli, P. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nature Cell Biol. 1, 33–39 (1999)

    CAS  Article  Google Scholar 

  16. 16

    Farsad, K. et al. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J. Cell Biol. 155, 193–200 (2001)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Danino, D., Moon, K. H. & Hinshaw, J. E. Rapid constriction of lipid bilayers by the mechanochemical enzyme dynamin. J. Struct. Biol. 147, 259–267 (2004)

    CAS  Article  PubMed  Google Scholar 

  18. 18

    Tsafrir, I., Caspi, Y., Guedeau-Boudeville, M. A., Arzi, T. & Stavans, J. Budding and tubulation in highly oblate vesicles by anchored amphiphilic molecules. Phys. Rev. Lett. 91, 138102 (2003)

    ADS  Article  PubMed  Google Scholar 

  19. 19

    Roux, A. et al. A minimal system allowing tubulation with molecular motors pulling on giant liposomes. Proc. Natl Acad. Sci. USA 99, 5394–5399 (2002)

    ADS  CAS  Article  PubMed  Google Scholar 

  20. 20

    Leduc, C. et al. Cooperative extraction of membrane nanotubes by molecular motors. Proc. Natl Acad. Sci. USA 101, 17096–17101 (2004)

    ADS  CAS  Article  PubMed  Google Scholar 

  21. 21

    Chen, Y. J., Zhang, P., Egelman, E. H. & Hinshaw, J. E. The stalk region of dynamin drives the constriction of dynamin tubes. Nature Struct. Mol. Biol. 11, 574–575 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Shpetner, H. S. & Vallee, R. B. Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules. Cell 59, 421–432 (1989)

    CAS  Article  PubMed  Google Scholar 

  23. 23

    Obar, R. A., Collins, C. A., Hammarback, J. A., Shpetner, H. S. & Vallee, R. B. Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins. Nature 347, 256–261 (1990)

    ADS  CAS  Article  PubMed  Google Scholar 

  24. 24

    Zhang, P. & Hinshaw, J. E. Three-dimensional reconstruction of dynamin in the constricted state. Nature Cell Biol. 3, 922–926 (2001)

    CAS  Article  PubMed  Google Scholar 

  25. 25

    Charvin, G., Bensimon, D. & Croquette, V. Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases. Proc. Natl Acad. Sci. USA 100, 9820–9825 (2003)

    ADS  CAS  Article  PubMed  Google Scholar 

  26. 26

    Orth, J. D. & McNiven, M. A. Dynamin at the actin–membrane interface. Curr. Opin. Cell Biol. 15, 31–39 (2003)

    CAS  Article  PubMed  Google Scholar 

  27. 27

    Schafer, D. A. Regulating actin dynamics at membranes: a focus on dynamin. Traffic 5, 463–469 (2004)

    CAS  Article  PubMed  Google Scholar 

  28. 28

    Kaksonen, M., Toret, C. P. & Drubin, D. G. A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell 123, 305–320 (2005)

    CAS  Article  Google Scholar 

  29. 29

    Roux, A. et al. Role of curvature and phase transition in lipid sorting and fission of membrane tubules. EMBO J. 24, 1537–1545 (2005)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Moscho, A., Orwar, O., Chiu, D. T., Modi, B. P. & Zare, R. N. Rapid preparation of giant unilamellar vesicles. Proc. Natl Acad. Sci. USA 93, 11443–11447 (1996)

    ADS  CAS  Article  PubMed  Google Scholar 

Download references


We thank V. Unger, G. Di Paolo, M. Solimena and K. Erdmann for discussion and critical reading of this manuscript. We thank F. Wilson for technical support. This work was supported by National Institutes of Health grants and a G. Harold and Leila Y. Mathers Charitable Foundation grant to P.D.C. A.R. was supported by the European Molecular Biology Organization (EMBO) Long-Term Postdoctoral Fellowship programme and the Cross-Disciplinary Fellowship programme of the Human Frontier Science Program (HFSP).Author Contributions A.R. and P.D.C. conceived the project, designed the experiments and evaluated the results. A.R. performed the experiments alone, with the exception of the giant-liposome assay (K.U. and A.R.) and electron microscopy (A.F., K.U. and A.R.). A.R. and P.D.C. wrote the paper.

Author information



Corresponding author

Correspondence to Pietro De Camilli.

Ethics declarations

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods, Supplementary Figures 1–5 and Supplementary Movie Legends. (PDF 1200 kb)

Supplementary Movie 1

Growth of dynamin coated tubules on sheets of lipid membranes observed by DIC microscopy. Speed, 30X. (AVI 8910 kb)

Supplementary Movie 2

Effect of 1 mM GTP on a network of dynamin-coated lipid tubules. Real-time (15 fps) DIC microscopy. (AVI 3846 kb)

Supplementary Movie 3

Effect of 1 mM GTP on a dynamin-coated lipid tubule anchored at static point at both ends. Real-time (15 fps) DIC microscopy. (AVI 2852 kb)

Supplementary Movie 4

Effect of 1 mM GTP on a dynamin-coated lipid tubule free to retract. Real-time (15 fps) DIC microscopy. (AVI 1644 kb)

Supplementary Movie 5

Effect of 1 mM GTP, in the absence of ATP, on membrane tubules generated from giant liposomes by kinesin on microtubules and subsequently coated with dynamin. Speed, 60X (AVI 1860 kb)

Supplementary Movie 6

Effect of 1mg/ml dynamin co-added with 0.5 mM GTP in the presence of ATP on membrane tubules generated by kinesin on microtubules. Speed, 15X (AVI 9278 kb)

Supplementary Movie 7

1 mM GTP induces supercoiling of loops of dynamin-coated tubules. Same field as Fig. 4a. Real-time (15 fps) DIC microscopy. (AVI 1386 kb)

Supplementary Movie 8

Rotation of a streptavidin bead (diameter 260 nm) attached to a biotin-dynamin coated tubule after addition of 200 μM GTP. Real time (30fps). (AVI 8750 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Roux, A., Uyhazi, K., Frost, A. et al. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Nature 441, 528–531 (2006).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing