dynamins

Summary

Summary: A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.

Top Publications

  1. Pawlowski N. Dynamin self-assembly and the vesicle scission mechanism: how dynamin oligomers cleave the membrane neck of clathrin-coated pits during endocytosis. Bioessays. 2010;32:1033-9 pubmed publisher
    ..The oligomerisation of two other dynamin superfamily proteins, the guanylate binding proteins (GBPs) and the immunity-related GTPases (IRGs), is addressed briefly. ..
  2. Rambold A, Kostelecky B, Elia N, Lippincott Schwartz J. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A. 2011;108:10190-5 pubmed publisher
  3. Pentecost M, Kumaran J, Ghosh P, Amieva M. Listeria monocytogenes internalin B activates junctional endocytosis to accelerate intestinal invasion. PLoS Pathog. 2010;6:e1000900 pubmed publisher
  4. He B, Yu X, Margolis M, Liu X, Leng X, Etzion Y, et al. Live-cell imaging in Caenorhabditis elegans reveals the distinct roles of dynamin self-assembly and guanosine triphosphate hydrolysis in the removal of apoptotic cells. Mol Biol Cell. 2010;21:610-29 pubmed publisher
    b>Dynamins are large GTPases that oligomerize along membranes. Dynamin's membrane fission activity is believed to underlie many of its physiological functions in membrane trafficking...
  5. Logsdon L, Hakansson A, Cortés G, Wessels M. Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. MBio. 2011;2:e00332-10 pubmed publisher
    ..We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway. ..
  6. Yu T, Jhun B, Yoon Y. High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid Redox Signal. 2011;14:425-37 pubmed publisher
    ..These results demonstrate that high-glucose stimulation induces the activation of mitochondrial fission via signals mediated by intracellular Ca(2+) and ERK1/2. ..
  7. Otto G, Nichols B. The roles of flotillin microdomains--endocytosis and beyond. J Cell Sci. 2011;124:3933-40 pubmed publisher
    ..Finally, we will focus on the questions that are raised by these new experiments and their implications for future studies...
  8. Harper C, Martin S, Nguyen T, Daniels S, Lavidis N, Popoff M, et al. Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism. J Biol Chem. 2011;286:35966-76 pubmed publisher
    ..Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms. ..
  9. Odell L, Howan D, Gordon C, Robertson M, Chau N, Mariana A, et al. The pthaladyns: GTP competitive inhibitors of dynamin I and II GTPase derived from virtual screening. J Med Chem. 2010;53:5267-80 pubmed publisher
    ..9 microM. This compound was also competitive with respect to Mg(2+).GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis. ..

More Information

Publications62

  1. Tanaka A, Cleland M, Xu S, Narendra D, Suen D, Karbowski M, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191:1367-80 pubmed publisher
    ..Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. ..
  2. Kageyama Y, Zhang Z, Sesaki H. Mitochondrial division: molecular machinery and physiological functions. Curr Opin Cell Biol. 2011;23:427-34 pubmed publisher
    ..We summarize recent progress in understanding how the division machinery assembles onto mitochondria and how mitochondrial division contributes to cellular physiology and human diseases. ..
  3. Chang C, Blackstone C. Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci. 2010;1201:34-9 pubmed publisher
    ..We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. ..
  4. Schmid S, Frolov V. Dynamin: functional design of a membrane fission catalyst. Annu Rev Cell Dev Biol. 2011;27:79-105 pubmed publisher
  5. Ferguson S, De Camilli P. Dynamin, a membrane-remodelling GTPase. Nat Rev Mol Cell Biol. 2012;13:75-88 pubmed publisher
    ..In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues. ..
  6. Peng L, Men X, Zhang W, Wang H, Xu S, Xu M, et al. Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic ?-cell apoptosis. Int J Mol Med. 2011;28:161-9 pubmed publisher
    ..These results indicate that DRP-1 mediates ER stress-induced pancreatic ?-cell apoptosis. ..
  7. Merrill R, Dagda R, Dickey A, Cribbs J, Green S, Usachev Y, et al. Mechanism of neuroprotective mitochondrial remodeling by PKA/AKAP1. PLoS Biol. 2011;9:e1000612 pubmed publisher
    ..Unopposed fusion then promotes formation of a mitochondrial reticulum, which protects neurons from diverse insults. ..
  8. Chircop M, Perera S, Mariana A, Lau H, Ma M, Gilbert J, et al. Inhibition of dynamin by dynole 34-2 induces cell death following cytokinesis failure in cancer cells. Mol Cancer Ther. 2011;10:1553-62 pubmed publisher
    ..Thus, the dynoles are a second class of dynamin GTPase inhibitors, with dynole 34-2 as the lead compound, that are novel antimitotic compounds acting specifically at the abscission stage. ..
  9. Mattheyses A, Atkinson C, Simon S. Imaging single endocytic events reveals diversity in clathrin, dynamin and vesicle dynamics. Traffic. 2011;12:1394-406 pubmed publisher
    ..These results illustrate the heterogeneity of behaviors of endocytic vesicles and the importance of establishing suitable evaluation criteria for biophysical processes...
  10. Kawauchi T, Sekine K, Shikanai M, Chihama K, Tomita K, Kubo K, et al. Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking. Neuron. 2010;67:588-602 pubmed publisher
    ..Taken together, our findings reveal physiological roles of endocytic pathways, each of which has specific functions in distinct steps of neuronal migration and maturation during mammalian brain formation...
  11. Joshi S, Perera S, Gilbert J, Smith C, Mariana A, Gordon C, et al. The dynamin inhibitors MiTMAB and OcTMAB induce cytokinesis failure and inhibit cell proliferation in human cancer cells. Mol Cancer Ther. 2010;9:1995-2006 pubmed publisher
    ..Thus, MiTMABs have toxicity and antiproliferative properties that preferentially target cancer cells. This suggests that dynII may be a novel target for pharmacologic intervention for the treatment of cancer. ..
  12. Richard J, Leikina E, Langen R, Henne W, Popova M, Balla T, et al. Intracellular curvature-generating proteins in cell-to-cell fusion. Biochem J. 2011;440:185-93 pubmed publisher
    ..Our findings indicate that fusion pore expansion at late stages of cell-to-cell fusion is mediated, directly or indirectly, by intracellular membrane-shaping proteins. ..
  13. Losón O, Song Z, Chen H, Chan D. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell. 2013;24:659-67 pubmed publisher
    ..Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission. ..
  14. Taylor M, Perrais D, Merrifield C. A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLoS Biol. 2011;9:e1000604 pubmed publisher
  15. Liu Y, Mattila J, Schmid S. Dynamin-catalyzed membrane fission requires coordinated GTP hydrolysis. PLoS ONE. 2013;8:e55691 pubmed publisher
    ..These studies establish that efficient fission from supported bilayers with excess membrane reservoir (SUPER) templates requires coordinated GTP hydrolysis across two rungs of an assembled dynamin collar. ..
  16. Bui H, Shaw J. Dynamin assembly strategies and adaptor proteins in mitochondrial fission. Curr Biol. 2013;23:R891-9 pubmed publisher
    ..and structural studies have revealed variations in the assembly properties of classical and mitochondrial dynamins that accommodate these differences...
  17. Liu J, Sun Y, Oster G, Drubin D. Mechanochemical crosstalk during endocytic vesicle formation. Curr Opin Cell Biol. 2010;22:36-43 pubmed publisher
    ..We mainly focus on clathrin-mediated and actin-mediated endocytosis in yeast and in mammalian cells. We further speculate on how mechanochemical feedback could modulate other membrane-remodeling processes. ..
  18. Ramachandran R. Vesicle scission: dynamin. Semin Cell Dev Biol. 2011;22:10-7 pubmed publisher
    ..Coordinated functions of BAR domain-containing binding partners are also discussed. ..
  19. Gao S, von der Malsburg A, Paeschke S, Behlke J, Haller O, Kochs G, et al. Structural basis of oligomerization in the stalk region of dynamin-like MxA. Nature. 2010;465:502-6 pubmed publisher
  20. Sandvig K, Pust S, Skotland T, van Deurs B. Clathrin-independent endocytosis: mechanisms and function. Curr Opin Cell Biol. 2011;23:413-20 pubmed publisher
  21. Liu Y, Neumann S, Ramachandran R, Ferguson S, Pucadyil T, Schmid S. Differential curvature sensing and generating activities of dynamin isoforms provide opportunities for tissue-specific regulation. Proc Natl Acad Sci U S A. 2011;108:E234-42 pubmed publisher
    ..These domains are specific to classical dynamins and are involved in regulating their activity...
  22. Sousa L, Lax I, Shen H, Ferguson S, De Camilli P, Schlessinger J. Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane. Proc Natl Acad Sci U S A. 2012;109:4419-24 pubmed publisher
  23. Ong S, Subrayan S, Lim S, Yellon D, Davidson S, Hausenloy D. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121:2012-22 pubmed publisher
    ..0+/-4.5% in control; n=6 animals per group; P<0.05). Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury, suggesting a novel pharmacological strategy for cardioprotection. ..
  24. von Kleist L, Stahlschmidt W, Bulut H, Gromova K, Puchkov D, Robertson M, et al. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell. 2011;146:471-84 pubmed publisher
    ..Pitstops provide new tools to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry and as modulators of cell signaling. ..
  25. Wang X, Su B, Liu W, He X, Gao Y, Castellani R, et al. DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson's disease. Aging Cell. 2011;10:807-23 pubmed publisher
    ..Overall, these findings suggest that DLP1-dependent mitochondrial fragmentation plays a crucial role in mediating MPP(+) -induced mitochondria abnormalities and cellular dysfunction and may represent a novel therapeutic target for PD. ..
  26. McMahon H, Boucrot E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol. 2011;12:517-33 pubmed publisher
    ..Some modules can be used in other pathways, and additions or substitutions confer cell specificity and adaptability. ..
  27. De Palma C, Falcone S, Pisoni S, Cipolat S, Panzeri C, Pambianco S, et al. Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation. Cell Death Differ. 2010;17:1684-96 pubmed publisher
    ..These data uncover a novel level of regulation of differentiation linking mitochondrial morphology and function to myogenic differentiation. ..
  28. Conery A, Sever S, Harlow E. Nucleoside diphosphate kinase Nm23-H1 regulates chromosomal stability by activating the GTPase dynamin during cytokinesis. Proc Natl Acad Sci U S A. 2010;107:15461-6 pubmed publisher
    ..We thus provide evidence that the loss of Nm23-H1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability. ..
  29. Lu N, Shen Q, Mahoney T, Liu X, Zhou Z. Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling. Mol Biol Cell. 2011;22:354-74 pubmed publisher
  30. Ai E, Poole D, Skop A. Long astral microtubules and RACK-1 stabilize polarity domains during maintenance phase in Caenorhabditis elegans embryos. PLoS ONE. 2011;6:e19020 pubmed publisher
    ..We found a correlation between short astral microtubules and the instability of PAR-6 and PAR-2 domains during maintenance phase. Our data support a necessary role for astral microtubules in the maintenance phase of cell polarity. ..
  31. Low H, Lowe J. Dynamin architecture--from monomer to polymer. Curr Opin Struct Biol. 2010;20:791-8 pubmed publisher
    b>Dynamins form a family of eukaryotic and prokaryotic proteins involved in membrane fission, fusion and restructuring. They have complex mechanisms of self-assembly, which are coupled to the tubulation and destabilization of lipid bilayers...
  32. Kumari S, Mg S, Mayor S. Endocytosis unplugged: multiple ways to enter the cell. Cell Res. 2010;20:256-75 pubmed publisher
    ..Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla. ..
  33. Faelber K, Held M, Gao S, Posor Y, Haucke V, Noe F, et al. Structural insights into dynamin-mediated membrane fission. Structure. 2012;20:1621-8 pubmed publisher
    ..Based on these data, we propose a structure-based model for dynamin-mediated scission of membranes. ..
  34. Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, et al. Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol. 2012;197:535-51 pubmed publisher
    ..Our findings suggest that mitochondrial division serves as a quality control mechanism to suppress oxidative damage and thus promote neuronal survival. ..
  35. Wu M, Huang B, Graham M, Raimondi A, Heuser J, Zhuang X, et al. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nat Cell Biol. 2010;12:902-8 pubmed publisher
    ..They also show that clathrin spatially directs plasma membrane invaginations that lead to the generation of endocytic vesicles larger than those enclosed by the coat...
  36. Pust S, Barth H, Sandvig K. Clostridium botulinum C2 toxin is internalized by clathrin- and Rho-dependent mechanisms. Cell Microbiol. 2010;12:1809-20 pubmed publisher
    ..Finally, we found evidence for a Rho-mediated uptake of C2 toxin. In conclusion, C2 toxin is endocytosed by dynamin-dependent mechanisms and we provide evidence for involvement of clathrin and Rho...
  37. Anantharam A, Axelrod D, Holz R. Real-time imaging of plasma membrane deformations reveals pre-fusion membrane curvature changes and a role for dynamin in the regulation of fusion pore expansion. J Neurochem. 2012;122:661-71 pubmed publisher
    ..Finally, we discuss how expansion of the fusion pore may be regulated by the GTPase activity of dynamin. ..
  38. Palmer C, Elgass K, Parton R, Osellame L, Stojanovski D, Ryan M. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem. 2013;288:27584-93 pubmed publisher
    ..We conclude that MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and suggest that they provide specificity to the division of mitochondria. ..
  39. Koirala S, Guo Q, Kalia R, Bui H, Eckert D, Frost A, et al. Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission. Proc Natl Acad Sci U S A. 2013;110:E1342-51 pubmed publisher
    ..This result demonstrates that an adaptor protein alters the architecture of a mitochondrial dynamin GTPase polymer in a manner that could facilitate membrane constriction and severing activity. ..
  40. Reid A, Lord T, Stanger S, Roman S, McCluskey A, Robinson P, et al. Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa. J Biol Chem. 2012;287:37659-72 pubmed publisher
    ..On the basis of our collective data, we propose that dynamin could regulate specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa. ..
  41. Smaczynska de Rooij I, Allwood E, Aghamohammadzadeh S, Hettema E, Goldberg M, Ayscough K. A role for the dynamin-like protein Vps1 during endocytosis in yeast. J Cell Sci. 2010;123:3496-506 pubmed publisher
    b>Dynamins are a conserved family of proteins involved in membrane fusion and fission...
  42. Rai A, Nöthe H, Tzvetkov N, Korenbaum E, Manstein D. Dictyostelium dynamin B modulates cytoskeletal structures and membranous organelles. Cell Mol Life Sci. 2011;68:2751-67 pubmed publisher
    ..Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related proteins.
  43. Chakraborty S, Hosur R. NMR insights into the core of GED assembly by H/D exchange coupled with DMSO dissociation and analysis of the denatured state. J Mol Biol. 2011;405:1202-14 pubmed publisher
    ..These domains would identify folding and association initiation sites of GED. Interestingly, they also coincide with the helical domain in the native state, suggesting that helix formation leads to self-association of GED. ..
  44. Morlot S, Roux A. Mechanics of dynamin-mediated membrane fission. Annu Rev Biophys. 2013;42:629-49 pubmed publisher
    ..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. ..
  45. Chan D. Fusion and fission: interlinked processes critical for mitochondrial health. Annu Rev Genet. 2012;46:265-87 pubmed publisher
    ..A better understanding of these processes likely will ultimately lead to improvements in human health. ..
  46. Roux A, Koster G, Lenz M, Sorre B, Manneville J, Nassoy P, et al. Membrane curvature controls dynamin polymerization. Proc Natl Acad Sci U S A. 2010;107:4141-6 pubmed publisher
    ..More generally, we expect that any protein that binds or self-assembles onto membranes in a curvature-coupled way should behave in a qualitatively similar manner, but with its own specific range of concentration. ..
  47. Meinecke M, Boucrot E, Camdere G, Hon W, Mittal R, McMahon H. Cooperative recruitment of dynamin and BIN/amphiphysin/Rvs (BAR) domain-containing proteins leads to GTP-dependent membrane scission. J Biol Chem. 2013;288:6651-61 pubmed publisher
    ..Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. Thus, BAR domain proteins and dynamin act in synergy in membrane recruitment and GTP-dependent vesicle scission. ..
  48. Hawthorne A, Wylie C, Landmesser L, Deneris E, Silver J. Serotonergic neurons migrate radially through the neuroepithelium by dynamin-mediated somal translocation. J Neurosci. 2010;30:420-30 pubmed publisher
    ..Here we show for the first time that serotonergic neurons migrate by somal translocation mediated, in part, by dynamin. ..
  49. Joshi S, Braithwaite A, Robinson P, Chircop M. Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression. Mol Cancer. 2011;10:78 pubmed publisher
    ..This suggests that dynamin and potentially other cytokinesis factors are novel targets for development of cancer therapeutics. ..
  50. Zhang Z, Wakabayashi N, Wakabayashi J, Tamura Y, Song W, Sereda S, et al. The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol Biol Cell. 2011;22:2235-45 pubmed publisher
    ..Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells...
  51. Bürmann F, Ebert N, van Baarle S, Bramkamp M. A bacterial dynamin-like protein mediating nucleotide-independent membrane fusion. Mol Microbiol. 2011;79:1294-304 pubmed publisher
    b>Dynamins are a family of large GTPases that are involved in key cellular processes, where they mediate events of membrane fission and fusion...
  52. Douthitt H, Luo F, McCann S, Meriney S. Dynasore, an inhibitor of dynamin, increases the probability of transmitter release. Neuroscience. 2011;172:187-95 pubmed publisher
    ..Therefore, in interpreting effects of the dynamin inhibitor dynasore at synapses, one must be alert to potential increases in presynaptic calcium concentration and transmitter release probability. ..
  53. Gu C, Yaddanapudi S, Weins A, Osborn T, Reiser J, Pollak M, et al. Direct dynamin-actin interactions regulate the actin cytoskeleton. EMBO J. 2010;29:3593-606 pubmed publisher
    ..Together, our results support a model in which assembled dynamin, generated through interactions with short actin filaments, promotes actin polymerization via displacement of actin-CPs. ..