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Gene Review

Dnm1  -  dynamin 1

Rattus norvegicus

Synonyms: B-dynamin, D100, Dnm, Dynamin, brain, Dynamin-1
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Disease relevance of Dnm1


Psychiatry related information on Dnm1

  • Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain [6].
  • 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 [7].

High impact information on Dnm1

  • Clathrin-coated buds and dynamin-coated tubules morphologically similar to corresponding structures observed in synaptic membranes can be generated on protein-free liposomes by incubation with cytosol, or with clathrin coat proteins and purified dynamin, respectively [8].
  • Dynamin GTPase activity is stimulated by several of the bound SH3 domains, suggesting that the function of the SH3 module is not restricted to protein-protein interactions but may also include the interactive regulation of GTP-binding proteins [9].
  • Synaptojanin is a nerve terminal protein of relative molecular mass 145,000 which appears to participate with dynamin in synaptic vesicle recycling [10].
  • Dynamin is a GTPase implicated in synaptic vesicle endocytosis and here we show that the walls of these membranous tubules, but not their distal ends, were positive for dynamin immunoreactivity [11].
  • These findings demonstrate that dynamin and clathrin act at different sites in the formation of endocytic vesicles [11].

Chemical compound and disease context of Dnm1


Biological context of Dnm1

  • Dynamin is a 100-kDa microtubule-activated GTPase originally isolated from mammalian brain that has been proposed to be crucial in the early steps of endocytosis [14].
  • Endophilin-SH3 binding to the high affinity site was disrupted when dynamin-1 PRD was phosphorylated with Cdk5, indicating that this site overlaps the phosphorylation sites, but amphiphysin-SH3 binding was unaffected [15].
  • Other SH3 domains showed similarly complex binding characteristics, and substantial differences were noted between the PRDs from dynamin-1 and -2 [15].
  • Preloading of dynamin-1 PRD with the amphiphysin-SH3 domain partially occluded binding of the endophilin-SH3 domain, indicating overlap between the binding sites in the C terminus, but endophilin was still able to interact with the high affinity N-terminal site [15].
  • To assess the specificity and kinetics of this process, we undertook surface plasmon resonance studies of the interaction between isolated PRDs of dynamin-1 and -2 and several purified SH3 domains [15].

Anatomical context of Dnm1


Associations of Dnm1 with chemical compounds

  • Glutathione S-transferase-linked SH3 domains bound with high affinity (K(D) approximately 10 nm to 1 microm) to both dynamin-1 and -2 [15].
  • These include the clathrin-coated buds and dynamin-coated tubules, which accumulate in nerve terminal membranes incubated in the presence of guanosine 5'-3-O-(thio)triphosphate [20].
  • Thus, c-Src-mediated tyrosine phosphorylation is required for the function of dynamin in ligand-induced signaling receptor internalization [21].
  • Because fission of clathrin-coated pits requires dynamin, we examined the mechanisms by which dopamine receptor signals promote dynamin-2 recruitment and assembly at the site of Na(+),K(+)-ATPase endocytosis [22].
  • Dephosphorylation of amphiphysin I, like dephosphorylation of dynamin I and synaptojanin I, is inhibited by cyclosporin A and FK-506 (0.5 microM), two drugs that specifically block the Ca2+/calmodulin-dependent phosphatase 2B calcineurin, but not by okadaic acid (1 microM), which blocks protein phosphatases 1 and 2B [20].

Physical interactions of Dnm1


Enzymatic interactions of Dnm1


Co-localisations of Dnm1


Regulatory relationships of Dnm1


Other interactions of Dnm1


Analytical, diagnostic and therapeutic context of Dnm1


  1. Sweeping model of dynamin activity. Visualization of coupling between exocytosis and endocytosis under an evanescent wave microscope with green fluorescent proteins. Tsuboi, T., Terakawa, S., Scalettar, B.A., Fantus, C., Roder, J., Jeromin, A. J. Biol. Chem. (2002) [Pubmed]
  2. Expression and purification of dynamin II domains and initial studies on structure and function. Dong, J., Misselwitz, R., Welfle, H., Westermann, P. Protein Expr. Purif. (2000) [Pubmed]
  3. Calcium- and dynamin-independent endocytosis in dorsal root ganglion neurons. Zhang, C., Xiong, W., Zheng, H., Wang, L., Lu, B., Zhou, Z. Neuron (2004) [Pubmed]
  4. Dynamin 1 antisense oligonucleotide treatment prevents neurite formation in cultured hippocampal neurons. Torre, E., McNiven, M.A., Urrutia, R. J. Biol. Chem. (1994) [Pubmed]
  5. Receptor-mediated Moloney murine leukemia virus entry can occur independently of the clathrin-coated-pit-mediated endocytic pathway. Lee, S., Zhao, Y., Anderson, W.F. J. Virol. (1999) [Pubmed]
  6. Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain. García-Fuster, M.J., Ferrer-Alcón, M., Miralles, A., García-Sevilla, J.A. Naunyn Schmiedebergs Arch. Pharmacol. (2003) [Pubmed]
  7. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Roux, A., Uyhazi, K., Frost, A., De Camilli, P. Nature (2006) [Pubmed]
  8. Generation of coated intermediates of clathrin-mediated endocytosis on protein-free liposomes. Takei, K., Haucke, V., Slepnev, V., Farsad, K., Salazar, M., Chen, H., De Camilli, P. Cell (1998) [Pubmed]
  9. The GTPase dynamin binds to and is activated by a subset of SH3 domains. Gout, I., Dhand, R., Hiles, I.D., Fry, M.J., Panayotou, G., Das, P., Truong, O., Totty, N.F., Hsuan, J., Booker, G.W. Cell (1993) [Pubmed]
  10. A presynaptic inositol-5-phosphatase. McPherson, P.S., Garcia, E.P., Slepnev, V.I., David, C., Zhang, X., Grabs, D., Sossin, W.S., Bauerfeind, R., Nemoto, Y., De Camilli, P. Nature (1996) [Pubmed]
  11. Tubular membrane invaginations coated by dynamin rings are induced by GTP-gamma S in nerve terminals. Takei, K., McPherson, P.S., Schmid, S.L., De Camilli, P. Nature (1995) [Pubmed]
  12. Mu-opioid agonist inhibition of kappa-opioid receptor-stimulated extracellular signal-regulated kinase phosphorylation is dynamin-dependent in C6 glioma cells. Bohn, L.M., Belcheva, M.M., Coscia, C.J. J. Neurochem. (2000) [Pubmed]
  13. L-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced diabetic rat. Heo, Y.R., Kang, C.W., Cha, Y.S. J. Nutr. Sci. Vitaminol. (2001) [Pubmed]
  14. Identification of dynamin 2, an isoform ubiquitously expressed in rat tissues. Cook, T.A., Urrutia, R., McNiven, M.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation. Solomaha, E., Szeto, F.L., Yousef, M.A., Palfrey, H.C. J. Biol. Chem. (2005) [Pubmed]
  16. Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis. Wigge, P., Köhler, K., Vallis, Y., Doyle, C.A., Owen, D., Hunt, S.P., McMahon, H.T. Mol. Biol. Cell (1997) [Pubmed]
  17. Evidence that dystroglycan is associated with dynamin and regulates endocytosis. Zhan, Y., Tremblay, M.R., Melian, N., Carbonetto, S. J. Biol. Chem. (2005) [Pubmed]
  18. Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer. Gray, N.W., Fourgeaud, L., Huang, B., Chen, J., Cao, H., Oswald, B.J., Hémar, A., McNiven, M.A. Curr. Biol. (2003) [Pubmed]
  19. Expression of the endocytic proteins dynamin and amphiphysin in rat gastric enterochromaffin-like cells. Zanner, R., Gratzl, M., Prinz, C. J. Cell. Sci. (2004) [Pubmed]
  20. Amphiphysin I is associated with coated endocytic intermediates and undergoes stimulation-dependent dephosphorylation in nerve terminals. Bauerfeind, R., Takei, K., De Camilli, P. J. Biol. Chem. (1997) [Pubmed]
  21. Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor. Ahn, S., Kim, J., Lucaveche, C.L., Reedy, M.C., Luttrell, L.M., Lefkowitz, R.J., Daaka, Y. J. Biol. Chem. (2002) [Pubmed]
  22. Relevance of dopamine signals anchoring dynamin-2 to the plasma membrane during Na+,K+-ATPase endocytosis. Efendiev, R., Yudowski, G.A., Zwiller, J., Leibiger, B., Katz, A.I., Berggren, P.O., Pedemonte, C.H., Leibiger, I.B., Bertorello, A.M. J. Biol. Chem. (2002) [Pubmed]
  23. Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Anggono, V., Smillie, K.J., Graham, M.E., Valova, V.A., Cousin, M.A., Robinson, P.J. Nat. Neurosci. (2006) [Pubmed]
  24. Crystal structure of the amphiphysin-2 SH3 domain and its role in the prevention of dynamin ring formation. Owen, D.J., Wigge, P., Vallis, Y., Moore, J.D., Evans, P.R., McMahon, H.T. EMBO J. (1998) [Pubmed]
  25. Mixed-lineage kinase 2-SH3 domain binds dynamin and greatly enhances activation of GTPase by phospholipid. Rasmussen, R.K., Rusak, J., Price, G., Robinson, P.J., Simpson, R.J., Dorow, D.S. Biochem. J. (1998) [Pubmed]
  26. Identification of Nck interacting proteins in vascular smooth muscle cells. Schmitz, U., Thömmes, K., Beier, I., Düsing, R., Vetter, H. Clin. Exp. Hypertens. (2004) [Pubmed]
  27. Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1 receptor. Schmidlin, F., Dery, O., DeFea, K.O., Slice, L., Patierno, S., Sternini, C., Grady, E.F., Bunnett, N.W. J. Biol. Chem. (2001) [Pubmed]
  28. Phospholipase C-gamma1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis. Choi, J.H., Park, J.B., Bae, S.S., Yun, S., Kim, H.S., Hong, W.P., Kim, I.S., Kim, J.H., Han, M.Y., Ryu, S.H., Patterson, R.L., Snyder, S.H., Suh, P.G. J. Cell. Sci. (2004) [Pubmed]
  29. A putative role for intramolecular regulatory mechanisms in the adaptor function of amphiphysin in endocytosis. Farsad, K., Slepnev, V., Ochoa, G., Daniell, L., Haucke, V., De Camilli, P., Hauke, V. Neuropharmacology (2003) [Pubmed]
  30. Essential role of dynamin in internalization of M2 muscarinic acetylcholine and angiotensin AT1A receptors. Werbonat, Y., Kleutges, N., Jakobs, K.H., van Koppen, C.J. J. Biol. Chem. (2000) [Pubmed]
  31. Protein phosphorylation and calcium uptake into rat forebrain synaptosomes: modulation by the sigma ligand, 1,3-ditolylguanidine. Brent, P.J., Herd, L., Saunders, H., Sim, A.T., Dunkley, P.R. J. Neurochem. (1997) [Pubmed]
  32. Differential expression of endophilin 1 and 2 dimers at central nervous system synapses. Ringstad, N., Nemoto, Y., De Camilli, P. J. Biol. Chem. (2001) [Pubmed]
  33. Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic cycle. Iguchi, H., Watanabe, M., Kamitani, A., Nagai, A., Hosoya, O., Tsutsui, K., Kumon, H. Acta Med. Okayama (2002) [Pubmed]
  34. Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins. Obar, R.A., Collins, C.A., Hammarback, J.A., Shpetner, H.S., Vallee, R.B. Nature (1990) [Pubmed]
  35. Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring. Stowell, M.H., Marks, B., Wigge, P., McMahon, H.T. Nat. Cell Biol. (1999) [Pubmed]
  36. Predominant and developmentally regulated expression of dynamin in neurons. Nakata, T., Iwamoto, A., Noda, Y., Takemura, R., Yoshikura, H., Hirokawa, N. Neuron (1991) [Pubmed]
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