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Gene Review

DNM2  -  dynamin 2

Homo sapiens

Synonyms: CMT2M, CMTDI1, CMTDIB, DI-CMTB, DYN2, ...
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Disease relevance of DNM2


High impact information on DNM2


Chemical compound and disease context of DNM2

  • This induction (24.4- and 6.5-fold, respectively) and viral uptake were significantly diminished by preincubation with antibody for Dynamin 2 but not for Coxsackie adenovirus receptor or for integrin alpha(v) [4].

Biological context of DNM2


Anatomical context of DNM2


Associations of DNM2 with chemical compounds

  • Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A [12].
  • Dynamin-2 associates with the dopamine receptor signalplex and regulates internalization of activated D2 receptors [13].
  • Using a cleavable biotin assay to quantify receptor internalization, we found that expression of dynamin-2 mutants defective in GTPase function virtually abolished agonist-induced D2R internalization [13].
  • Although they differ in their ability to inhibit rapid endocytosis in adrenal chromaffin cells, the dynamin-1 and dynamin-2 PH domains showed identical phosphoinositide binding specificities [14].
  • Nitric oxide promotes endothelial cell survival signaling through S-nitrosylation and activation of dynamin-2 [15].

Physical interactions of DNM2

  • Furthermore, we also observed that dynamin-2 coimmunoprecipitates with KDR and is required for EC signaling/survival [16].
  • In the cytosol, SNX9 is present in a 14.5 S complex containing dynamin-2 and an unidentified 41-kDa protein [17].

Co-localisations of DNM2


Regulatory relationships of DNM2

  • The results suggest that SNX9-dependent recruitment of Dyn2 to the membrane is regulated by an interaction between SNX9 and aldolase [7].
  • However, expression of dominant-negative dynamin-2 constructs inhibited uptake of clustered ICAM-1 [18].

Other interactions of DNM2

  • Regulated membrane recruitment of dynamin-2 mediated by sorting nexin 9 [7].
  • Regulatory role of dynamin-2 in VEGFR-2/KDR-mediated endothelial signaling [16].
  • During caveolar trafficking, NOSTRIN functions as an adaptor to recruit mediators such as dynamin-2 essential for membrane fission [19].
  • Furthermore, specific inhibition of dynamin-2 GTPase function by overexpression of a dominant negative construct, K44A, prevented the BK-mediated enrichment of eNOS-GFP within low buoyant density, caveolin-enriched fractions of eNOS-GFP ECV304 cell lysates [20].
  • Unlike the internalization of detergent-resistant membrane (DRM)-associated interleukin 2 receptor, endocytosis of DRM-associated GPI-APs is unaffected by inhibition of RhoA or dynamin 2 activity [21].

Analytical, diagnostic and therapeutic context of DNM2

  • Interestingly, the interaction between cortactin and dynamin 2 in cells was dependent on actin polymerization and was attenuated upon cell exposure to cytochalasin D as analyzed by immunofluorescence and immunoprecipitation [22].
  • Titration of the effects showed that GTP and GDP bound to a single class of non-interacting sites in dynamin tetramers with apparent dissociation constants (K(d)) values of 5.4 and 7.4 microM (dynamin-1) and 13.2 and 7.1 microM (dynamin-2) respectively [23].
  • Furthermore, gel overlay and immunoprecipitation indicated a direct interaction between gamma-tubulin and a 219-amino-acid middle domain of Dyn2 [24].
  • Moreover, viral uptake in LoVo tumor xenografts was significantly increased in s.c. tumors (10.9-fold) when adenovirus was given i.v. at 24 hours after tumor irradiation, coincident with an elevated Dynamin 2 expression in irradiated tumors [4].


  1. Mutations in dynamin 2 cause dominant centronuclear myopathy. Bitoun, M., Maugenre, S., Jeannet, P.Y., Lacène, E., Ferrer, X., Laforêt, P., Martin, J.J., Laporte, J., Lochmüller, H., Beggs, A.H., Fardeau, M., Eymard, B., Romero, N.B., Guicheney, P. Nat. Genet. (2005) [Pubmed]
  2. Dynamin-2 regulates oxidized low-density lipoprotein-induced apoptosis of vascular smooth muscle cell. Kashiwakura, Y., Watanabe, M., Kusumi, N., Sumiyoshi, K., Nasu, Y., Yamada, H., Sawamura, T., Kumon, H., Takei, K., Daida, H. Circulation (2004) [Pubmed]
  3. A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy. Tosch, V., Rohde, H.M., Tronch??re, H., Zanoteli, E., Monroy, N., Kretz, C., Dondaine, N., Payrastre, B., Mandel, J.L., Laporte, J. Hum. Mol. Genet. (2006) [Pubmed]
  4. Ionizing radiation-induced adenovirus infection is mediated by Dynamin 2. Qian, J., Yang, J., Dragovic, A.F., Abu-Isa, E., Lawrence, T.S., Zhang, M. Cancer Res. (2005) [Pubmed]
  5. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Züchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S.A., Speer, M.C., Stenger, J.E., Walizada, G., Zhu, D., Pericak-Vance, M.A., Nicholson, G., Timmerman, V., Vance, J.M. Nat. Genet. (2005) [Pubmed]
  6. Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Gomez, T.S., Hamann, M.J., McCarney, S., Savoy, D.N., Lubking, C.M., Heldebrant, M.P., Labno, C.M., McKean, D.J., McNiven, M.A., Burkhardt, J.K., Billadeau, D.D. Nat. Immunol. (2005) [Pubmed]
  7. Regulated membrane recruitment of dynamin-2 mediated by sorting nexin 9. Lundmark, R., Carlsson, S.R. J. Biol. Chem. (2004) [Pubmed]
  8. Evidence that dynamin-2 functions as a signal-transducing GTPase. Fish, K.N., Schmid, S.L., Damke, H. J. Cell Biol. (2000) [Pubmed]
  9. A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells. Krueger, E.W., Orth, J.D., Cao, H., McNiven, M.A. Mol. Biol. Cell (2003) [Pubmed]
  10. Differential regulation of interleukin 5-stimulated signaling pathways by dynamin. Gorska, M.M., Cen, O., Liang, Q., Stafford, S.J., Alam, R. J. Biol. Chem. (2006) [Pubmed]
  11. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Niemann, A., Berger, P., Suter, U. Neuromolecular Med. (2006) [Pubmed]
  12. Dynamin participates in focal extracellular matrix degradation by invasive cells. Baldassarre, M., Pompeo, A., Beznoussenko, G., Castaldi, C., Cortellino, S., McNiven, M.A., Luini, A., Buccione, R. Mol. Biol. Cell (2003) [Pubmed]
  13. Dynamin-2 associates with the dopamine receptor signalplex and regulates internalization of activated D2 receptors. Kabbani, N., Jeromin, A., Levenson, R. Cell. Signal. (2004) [Pubmed]
  14. The pleckstrin homology domains of dynamin isoforms require oligomerization for high affinity phosphoinositide binding. Klein, D.E., Lee, A., Frank, D.W., Marks, M.S., Lemmon, M.A. J. Biol. Chem. (1998) [Pubmed]
  15. Nitric oxide promotes endothelial cell survival signaling through S-nitrosylation and activation of dynamin-2. Kang-Decker, N., Cao, S., Chatterjee, S., Yao, J., Egan, L.J., Semela, D., Mukhopadhyay, D., Shah, V. J. Cell. Sci. (2007) [Pubmed]
  16. Regulatory role of dynamin-2 in VEGFR-2/KDR-mediated endothelial signaling. Bhattacharya, R., Kang-Decker, N., Hughes, D.A., Mukherjee, P., Shah, V., McNiven, M.A., Mukhopadhyay, D. FASEB J. (2005) [Pubmed]
  17. Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components. Lundmark, R., Carlsson, S.R. J. Biol. Chem. (2003) [Pubmed]
  18. A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. Muro, S., Wiewrodt, R., Thomas, A., Koniaris, L., Albelda, S.M., Muzykantov, V.R., Koval, M. J. Cell. Sci. (2003) [Pubmed]
  19. Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN. Schilling, K., Opitz, N., Wiesenthal, A., Oess, S., Tikkanen, R., Müller-Esterl, W., Icking, A. Mol. Biol. Cell (2006) [Pubmed]
  20. Inhibition of GTP-dependent vesicle trafficking impairs internalization of plasmalemmal eNOS and cellular nitric oxide production. Chatterjee, S., Cao, S., Peterson, T.E., Simari, R.D., Shah, V. J. Cell. Sci. (2003) [Pubmed]
  21. GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. Sabharanjak, S., Sharma, P., Parton, R.G., Mayor, S. Dev. Cell (2002) [Pubmed]
  22. Regulation of cortactin/dynamin interaction by actin polymerization during the fission of clathrin-coated pits. Zhu, J., Zhou, K., Hao, J.J., Liu, J., Smith, N., Zhan, X. J. Cell. Sci. (2005) [Pubmed]
  23. Conformational changes in dynamin on GTP binding and oligomerization reported by intrinsic and extrinsic fluorescence. Solomaha, E., Palfrey, H.C. Biochem. J. (2005) [Pubmed]
  24. Dynamin 2 binds gamma-tubulin and participates in centrosome cohesion. Thompson, H.M., Cao, H., Chen, J., Euteneuer, U., McNiven, M.A. Nat. Cell Biol. (2004) [Pubmed]
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