DNM1 explained
Dynamin-1 is a protein that in humans is encoded by the DNM1 gene.[1] [2]
Function
Dynamin possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the dynamin, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described.[3]
Role in disease
De novo mutations in DNM1 have been associated with a severe form of childhood epilepsy called developmental and epileptic encephalopathy. Most pathogenic variants are missense variants, and have been shown to impair synaptic vesicle endocytosis in a dominant negative manner.[4]
Interactions
DNM1 has been shown to interact with:
Further reading
- Sever S . Dynamin and endocytosis. . Curr. Opin. Cell Biol. . 14 . 4 . 463–7 . 2003 . 12383797 . 10.1016/S0955-0674(02)00347-2 .
- Wiejak J, Wyroba E . Dynamin: characteristics, mechanism of action and function. . Cell. Mol. Biol. Lett. . 7 . 4 . 1073–80 . 2003 . 12511974 .
- Orth JD, McNiven MA . Dynamin at the actin-membrane interface. . Curr. Opin. Cell Biol. . 15 . 1 . 31–9 . 2003 . 12517701 . 10.1016/S0955-0674(02)00010-8 .
- Timm D, Salim K, Gout I . Crystal structure of the pleckstrin homology domain from dynamin. . Nat. Struct. Biol. . 1 . 11 . 782–8 . 1995 . 7634088 . 10.1038/nsb1194-782 . 1454909 . etal.
- Downing AK, Driscoll PC, Gout I . Three-dimensional solution structure of the pleckstrin homology domain from dynamin. . Curr. Biol. . 4 . 10 . 884–91 . 1995 . 7850421 . 10.1016/S0960-9822(00)00197-4 . 37072095 . etal.
- Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB . Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin. . Cell . 79 . 2 . 199–209 . 1994 . 7954789 . 10.1016/0092-8674(94)90190-2 . 33767806 .
- van der Bliek AM, Redelmeier TE, Damke H . Mutations in human dynamin block an intermediate stage in coated vesicle formation. . J. Cell Biol. . 122 . 3 . 553–63 . 1993 . 8101525 . 10.1083/jcb.122.3.553 . 2119674 . etal.
- Miki H, Miura K, Matuoka K . Association of Ash/Grb-2 with dynamin through the Src homology 3 domain. . J. Biol. Chem. . 269 . 8 . 5489–92 . 1994 . 10.1016/S0021-9258(17)37484-7 . 8119878 . etal. free .
- Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
- Sontag JM, Fykse EM, Ushkaryov Y . Differential expression and regulation of multiple dynamins. . J. Biol. Chem. . 269 . 6 . 4547–54 . 1994 . 10.1016/S0021-9258(17)41812-6 . 8308025 . etal. free .
- Grabs D, Slepnev VI, Songyang Z . The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. . J. Biol. Chem. . 272 . 20 . 13419–25 . 1997 . 9148966 . 10.1074/jbc.272.20.13419 . etal. free.
- Ramjaun AR, Micheva KD, Bouchelet I, McPherson PS . Identification and characterization of a nerve terminal-enriched amphiphysin isoform. . J. Biol. Chem. . 272 . 26 . 16700–6 . 1997 . 9195986 . 10.1074/jbc.272.26.16700 . free .
- Ringstad N, Nemoto Y, De Camilli P . The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. . Proc. Natl. Acad. Sci. U.S.A. . 94 . 16 . 8569–74 . 1997 . 9238017 . 10.1073/pnas.94.16.8569 . 23017 . free . 1997PNAS...94.8569R .
- McMahon HT, Wigge P, Smith C . Clathrin interacts specifically with amphiphysin and is displaced by dynamin. . FEBS Lett. . 413 . 2 . 319–22 . 1997 . 9280305 . 10.1016/S0014-5793(97)00928-9 . 42520828 .
- Wigge P, Köhler K, Vallis Y . Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis. . Mol. Biol. Cell . 8 . 10 . 2003–15 . 1997 . 9348539 . 10.1091/mbc.8.10.2003. 25662 . etal.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
- Witke W, Podtelejnikov AV, Di Nardo A . In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly. . EMBO J. . 17 . 4 . 967–76 . 1998 . 9463375 . 10.1093/emboj/17.4.967 . 1170446 . etal.
- Slepnev VI, Ochoa GC, Butler MH . Role of phosphorylation in regulation of the assembly of endocytic coat complexes. . Science . 281 . 5378 . 821–4 . 1998 . 9694653 . 10.1126/science.281.5378.821 . 1998Sci...281..821S . etal.
Notes and References
- Obar RA, Collins CA, Hammarback JA, Shpetner HS, Vallee RB . Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins . Nature . 347 . 6290 . 256–61 . October 1990 . 2144893 . 10.1038/347256a0 . 1990Natur.347..256O . 4264539 .
- Newman-Smith ED, Shurland DL, van der Bliek AM . Assignment of the dynamin-1 gene (DNM1) to human chromosome 9q34 by fluorescence in situ hybridization and somatic cell hybrid analysis . Genomics . 41 . 2 . 286–9 . July 1997 . 9143509 . 10.1006/geno.1996.4596 .
- Web site: Entrez Gene: DNM1 dynamin 1.
- Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, Johnson MR, Frankel WN, Petrou S, Boumil RM, Goldstein DB . 6 . Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis . Neurology. Genetics . 1 . 1 . e4 . June 2015 . 27066543 . 10.1212/01.NXG.0000464295.65736.da . 4821085 .
- October 1997 . Micheva KD, Kay BK, McPherson PS . Synaptojanin forms two separate complexes in the nerve terminal. Interactions with endophilin and amphiphysin . J. Biol. Chem. . 272 . 43 . 27239–45 . 9341169 . 10.1074/jbc.272.43.27239. free .
- October 1997 . Wigge P, Köhler K, Vallis Y, Doyle CA, Owen D, Hunt SP, McMahon HT . Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis . Mol. Biol. Cell . 8 . 10 . 2003–15 . 9348539 . 25662 . 10.1091/mbc.8.10.2003.
- August 1997 . McMahon HT, Wigge P, Smith C . Clathrin interacts specifically with amphiphysin and is displaced by dynamin . FEBS Lett. . 413 . 2 . 319–22 . 9280305 . 10.1016/s0014-5793(97)00928-9. 42520828 .
- May 2002 . Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW . Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate . J. Biol. Chem. . 277 . 20 . 17597–604 . 11877424 . 10.1074/jbc.M111101200. free .
- May 1997 . Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, De Camilli P . The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence . J. Biol. Chem. . 272 . 20 . 13419–25 . 9148966 . 10.1074/jbc.272.20.13419. free.
- September 2004 . Kamioka Y, Fukuhara S, Sawa H, Nagashima K, Masuda M, Matsuda M, Mochizuki N . A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis . J. Biol. Chem. . 279 . 38 . 40091–9 . 15252009 . 10.1074/jbc.M404899200. free .
- February 1994 . Miki H, Miura K, Matuoka K, Nakata T, Hirokawa N, Orita S, Kaibuchi K, Takai Y, Takenawa T . Association of Ash/Grb-2 with dynamin through the Src homology 3 domain . J. Biol. Chem. . 269 . 8 . 5489–92 . 10.1016/S0021-9258(17)37484-7 . 8119878 . free .
- January 1997 . Sastry L, Cao T, King CR . Multiple Grb2-protein complexes in human cancer cells . Int. J. Cancer . 70 . 2 . 208–13 . 9009162 . 10.1002/(sici)1097-0215(19970117)70:2<208::aid-ijc12>3.0.co;2-e. 10317185 . free .
- January 1999 . Wunderlich L, Faragó A, Buday L . Characterization of interactions of Nck with Sos and dynamin . Cell. Signal. . 11 . 1 . 25–9 . 10206341 . 10.1016/s0898-6568(98)00027-8.
- December 2000 . Modregger J, Ritter B, Witter B, Paulsson M, Plomann M . All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis . J. Cell Sci. . 113 . 24. 4511–21 . 10.1242/jcs.113.24.4511 . 11082044 .
- February 2003 . Modregger J, Schmidt AA, Ritter B, Huttner WB, Plomann M . Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1 . J. Biol. Chem. . 278 . 6 . 4160–7 . 12456676 . 10.1074/jbc.M208568200. free .