Dynamin I (96kDa) Click on each domain for more info:

Dynamin is a large GTPase implicated in the budding and scission nascent vesi cles from parent membranes. Dynamin has been best studied in the context of clathrin-coated vesicle (CCV) budding from the plasma membrane, but it is also involved in budding of CCVs from other compartments, budding of caveoli, phagocytosis and vesicle cy cling at the synapse. A temperature sensitive mutant of dynamin was found in Drosophila (Shibire) where at the non-permissive temperature synaptic vesicle recycling is blocked and endocytic profiles that have not detached from the parent membrane accumula te.

The large GTPase dynamin plays an essential role in clathrin-coated vesicle scission from the parent membrane. The protein forms a helical collar around the neck of an invaginating clathrin-coated vesicle, where it may regulate, pinch or pop the vesicle from the parent membrane (see poppase movie and see pinchase movie). We have previously published evidence that on GTP hydrolysis dynamin spirals undergo a length-wise ex tension in vitro- which we believe drives the vesicle away from the membrane causing lipid fission (see Stowell et al 1999). Thus we favour the Poppase hypothesis.

To address the possibility that dynamin could be a regulator of vesicle scission we have expressed dynamin GTPase mutants in vivo and show that the GTP hydrolysis activity o f dynamin is coupled to a conformational change and that this activity of the protein is essential for vesicle scission (see Marks et al 2001).

There are 3 major ques tions that should still be answered:
A. How does oligomerisation stimulated GTPase activation occur?(see tubulin)
B. Why do dynamin-related proteins bind GTP and GDP with a low affinity compared to ras (see table under nucleotide affinities)?
C. If dynamin is really a mechanochemical GTPase how is GTPase activity coupled to a conformational change in the prote in?

Our publications on dynamin
Praefcke, G.J.K. and McMahon, H.T. (2004) The Dynamin Superfamily: Universal membrane tubulation and fission molecules? Nature Reviews in Molecular Cell Biology 5, 133-147 (abstract) (pdf)
Marks, B., Stowell, M., Vallis, Y., Mills, I., Gibson, A., Hopkins, C.R. and McMahon, H.T . (2001) GTPase activity of dynamin and resulting conformation change are essential for endocytosis. Nature. 410, 231-235 (abstra ct). (.pdf) (see picture story in Nature Structural Biology, April issue 8, 301)
Stowell, M.H.B., Marks, B., Wigge, P., and McMahon, H.T. (1999) Nucleotide-dependent conformational changes in dyna min: Evidence for a mechanochemical molecular spring. Nature Cell Biol. 1, 27-32 (abstract).
Vallis, Y., Wigge, P., Marks, B., Evans, P.R., and McMahon, H.T. (1999) Importance of the PH domain of dynamin in clathrin-mediated endocytosis. Current Biol. 9, 257-260 (abstract). (see also review in next issue)
Owen, D.J., Wigge, P. Vallis, Y., Moore, J.D.A., Evans, P.R. and McMahon H.T. (1998) Crystal structure of the amphiphysin-2 SH3 domain and its role in the prevention of dynamin ring formation. EMBO J. 17, 5273-5285 (abstract).
Marks, B. and McMahon, H.T. (1998) Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals . Current Biol. 8, 740-749 (abstract).
Wigge, P., Vallis, Y. and McMahon, H.T. (1997) Inhibition of receptor-mediated endocyto sis by the amphiphysin SH3 domain. Current Biol. 7, 554-560 (abstract).
McMahon, H.T., Wigge, P. and Smith, C. (1997) Clathrin interacts specifically with amphiphysin and is displaced by dynamin. FEBS Lett. 413, 319-322 (abstract).
Wigge, P., Köhler, K., Vallis, Y., Doyle, C.A., Owen, D., Hunt, S.P. and McMahon, H.T. (1997) Amphiphysin heterodimers: Potential role in clathrin-mediated endocytosis. Mol. Biol. Cell 8, 2003-2015 (abstract).

(These Dynamin Web pages have been written to accompany our review on the Dynamin Superfamily of proteins in Nature Reviews on Molecular Cell Biolog y 2004, 5, 133-147.. We do not wish these pages to be a catalogue for dynamin but rather a distillation of the literature with an emphasis on our viewpoint. We will aim to update these pages on a regular basis, Harvey.)