{{Short description|Vesicle formation GTPase family}} {{Infobox protein family | Symbol = Dynamin_N | Name = Dynamin family | image = PDB 2aka EBI.jpg | width = | caption = Structure of the nucleotide-free myosin II motor domain from ''Dictyostelium discoideum'' fused to the GTPase domain of dynamin I from ''Rattus norvegicus'' | Pfam = PF00350 | Pfam_clan = CL0023 | InterPro = IPR001401 | SMART = | PROSITE = PDOC00362 | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} {{Infobox protein family | Symbol = Dynamin_M | Name = Dynamin central region | image = PDB 2aka EBI.jpg | width = | caption = Structure of the nucleotide-free myosin II motor domain from ''Dictyostelium discoideum'' fused to the GTPase domain of dynamin I from ''Rattus norvegicus'' | Pfam = PF01031 | Pfam_clan = | InterPro = IPR000375 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Dynamin''' is a GTPase protein responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA1, mitofusins, and GBPs. Members of the dynamin family are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (particularly caveolae internalization) as well as at the Golgi apparatus.<ref name= Henley>{{Cite journal|title=Participation of dynamin in the biogenesis of cytoplasmic vesicles|first1=John R.|last1=Henley|first2=Hong|last2=Cao|first3=Mark A.|last3=McNiven|date=December 16, 1999|journal=The FASEB Journal|volume=13|issue=9002|pages=S243-7 |doi=10.1096/fasebj.13.9002.S243|doi-access=free |pmid=10619136 |s2cid=24401725 }}</ref><ref name= Hinshaw>Hinshaw, J. [http://www2.niddk.nih.gov/NIDDKLabs/IntramuralFaculty/HinshawJenny.htm "Research statement, Jenny E. Hinshaw, Ph.D."] {{Webarchive|url=https://web.archive.org/web/20210715052253/https://www.niddk.nih.gov/NIDDKLabs/IntramuralFaculty/HinshawJenny.htm |date=2021-07-15 }} National Institute of Diabetes & Digestive & Kidney Diseases, Laboratory of Cell Biochemistry and Biology. Accessed 19 March 2013.</ref><ref name= Urrutia>{{cite journal | vauthors = Urrutia R, Henley JR, Cook T, McNiven MA | title = The dynamins: redundant or distinct functions for an expanding family of related GTPases? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 2 | pages = 377–384 | date = January 1997 | pmid = 9012790 | pmc = 34135 | doi = 10.1073/pnas.94.2.377 | bibcode = 1997PNAS...94..377U | doi-access = free }}</ref> Dynamin family members also play a role in many processes including division of organelles,<ref name="pmid16218949">{{cite journal | vauthors = Thoms S, Erdmann R | title = Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation | journal = The FEBS Journal | volume = 272 | issue = 20 | pages = 5169–5181 | date = October 2005 | pmid = 16218949 | doi = 10.1111/j.1742-4658.2005.04939.x | doi-access = }}</ref> cytokinesis and microbial pathogen resistance.
== Structure == thumb|left|Dynamin assembled into helical polymers as visualized by negative stain electron microscopy.<ref>{{cite journal | vauthors = Hinshaw JE, Schmid SL | title = Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding | journal = Nature | volume = 374 | issue = 6518 | pages = 190–192 | date = March 1995 | pmid = 7877694 | doi = 10.1038/374190a0 | bibcode = 1995Natur.374..190H | s2cid = 4365628 }}</ref>|alt=
Dynamin itself is a 96 kDa enzyme, and was first isolated when researchers were attempting to isolate new microtubule-based motors from the bovine brain. Dynamin has been extensively studied in the context of clathrin-coated vesicle budding from the cell membrane.<ref name= Urrutia/><ref name= McMahon>{{cite journal | vauthors = Praefcke GJ, McMahon HT | title = The dynamin superfamily: universal membrane tubulation and fission molecules? | journal = Nature Reviews. Molecular Cell Biology | volume = 5 | issue = 2 | pages = 133–147 | date = February 2004 | pmid = 15040446 | doi = 10.1038/nrm1313 | s2cid = 6305282 }}</ref> Beginning from the N-terminus, Dynamin consists of a GTPase domain connected to a helical stalk domain via a flexible neck region containing a Bundle Signalling Element and [https://www.ebi.ac.uk/interpro/entry/IPR020850 GTPase Effector Domain]. At the opposite end of the stalk domain is a loop that links to a membrane-binding Pleckstrin homology domain. The protein strand then loops back towards the GTPase domain and terminates with a Proline Rich Domain that binds to the Src Homology domains of many proteins.
== Function ==
During clathrin-mediated endocytosis, the cell membrane invaginates to form a budding vesicle. Dynamin binds to and assembles around the neck of the endocytic vesicle, forming a helical polymer arranged such that the GTPase domains dimerize in an asymmetric manner across helical rungs.<ref>{{cite journal | vauthors = Sundborger AC, Fang S, Heymann JA, Ray P, Chappie JS, Hinshaw JE | title = A dynamin mutant defines a superconstricted prefission state | journal = Cell Reports | volume = 8 | issue = 3 | pages = 734–742 | date = August 2014 | pmid = 25088425 | pmc = 4142656 | doi = 10.1016/j.celrep.2014.06.054 }}</ref><ref name=":0" /> The polymer constricts the underlying membrane upon GTP binding and hydrolysis via conformational changes emanating from the flexible neck region that alters the overall helical symmetry.<ref name=":0">{{cite journal | vauthors = Kong L, Sochacki KA, Wang H, Fang S, Canagarajah B, Kehr AD, Rice WJ, Strub MP, Taraska JW, Hinshaw JE | display-authors = 6 | title = Cryo-EM of the dynamin polymer assembled on lipid membrane | journal = Nature | volume = 560 | issue = 7717 | pages = 258–262 | date = August 2018 | pmid = 30069048 | pmc = 6121775 | doi = 10.1038/s41586-018-0378-6 | bibcode = 2018Natur.560..258K }}</ref> Constriction around the vesicle neck leads to the formation of a hemi-fission membrane state that ultimately results in membrane scission.<ref name= Hinshaw/><ref name= McMahon/><ref>{{cite journal | vauthors = Mattila JP, Shnyrova AV, Sundborger AC, Hortelano ER, Fuhrmans M, Neumann S, Müller M, Hinshaw JE, Schmid SL, Frolov VA | display-authors = 6 | title = A hemi-fission intermediate links two mechanistically distinct stages of membrane fission | journal = Nature | volume = 524 | issue = 7563 | pages = 109–113 | date = August 2015 | pmid = 26123023 | pmc = 4529379 | doi = 10.1038/nature14509 | bibcode = 2015Natur.524..109M }}</ref> Constriction may be in part the result of the twisting activity of dynamin, which makes dynamin the only molecular motor known to have a twisting activity.<ref name= Roux>{{cite journal | vauthors = Roux A, Uyhazi K, Frost A, De Camilli P | title = GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission | journal = Nature | volume = 441 | issue = 7092 | pages = 528–531 | date = May 2006 | pmid = 16648839 | doi = 10.1038/nature04718 | bibcode = 2006Natur.441..528R | s2cid = 4413887 }}</ref>
==Types== In mammals, three different dynamin genes have been identified with key sequence differences in their Pleckstrin homology domains leading to differences in the recognition of lipid membranes:
* Dynamin I is expressed in neurons and neuroendocrine cells * Dynamin II is expressed in most cell types * Dynamin III is strongly expressed in the testis, but is also present in heart, brain, and lung tissue.<ref name= Henley/><ref name= McMahon/>
== Pharmacology == Small molecule inhibitors of dynamin activity have been developed, including Dynasore<ref>{{cite journal | vauthors = Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T | title = Dynasore, a cell-permeable inhibitor of dynamin | language = English | journal = Developmental Cell | volume = 10 | issue = 6 | pages = 839–850 | date = June 2006 | pmid = 16740485 | doi = 10.1016/j.devcel.2006.04.002 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Eschenburg S, Reubold TF | title = Modulation of dynamin function by small molecules | journal = Biological Chemistry | volume = 399 | issue = 12 | pages = 1421–1432 | date = November 2018 | pmid = 30067507 | doi = 10.1515/hsz-2018-0257 | s2cid = 51895475 | doi-access = free }}</ref> and photoswitchable derivatives (Dynazo)<ref>{{cite journal | vauthors = Camarero N, Trapero A, Pérez-Jiménez A, Macia E, Gomila-Juaneda A, Martín-Quirós A, Nevola L, Llobet A, Llebaria A, Hernando J, Giralt E, Gorostiza P | display-authors = 6 | title = Correction: Photoswitchable dynasore analogs to control endocytosis with light | journal = Chemical Science | volume = 11 | issue = 35 | pages = 9712 | date = September 2020 | pmid = 33016959 | pmc = 7495901 | doi = 10.1039/D0SC90189J }}</ref> for spatiotemporal control of endocytosis with light (photopharmacology).
== Disease implications == Mutations in Dynamin II have been found to cause dominant intermediate Charcot-Marie-Tooth disease.<ref>{{cite journal | vauthors = Züchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, Merory J, Oliveira SA, Speer MC, Stenger JE, Walizada G, Zhu D, Pericak-Vance MA, Nicholson G, Timmerman V, Vance JM | display-authors = 6 | title = Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease | journal = Nature Genetics | volume = 37 | issue = 3 | pages = 289–294 | date = March 2005 | pmid = 15731758 | doi = 10.1038/ng1514 | s2cid = 19191581 }}</ref> Epileptic encephalopathy–causing de novo mutations in dynamin have been suggested to cause dysfunction of vesicle scission during synaptic vesicle endocytosis.<ref name="Dhindsa">{{cite journal | vauthors = Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, Johnson MR, Frankel WN, Petrou S, Boumil RM, Goldstein DB | display-authors = 6 | title = Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis | journal = Neurology. Genetics | volume = 1 | issue = 1 | pages = e4 | date = June 2015 | pmid = 27066543 | pmc = 4821085 | doi = 10.1212/01.NXG.0000464295.65736.da }}</ref>
== References == {{reflist}}
== External links == {{Commons category|Dynamins}} * {{MeshName|Dynamins}}
{{Vesicular transport proteins}} {{Cytoskeletal Proteins}} {{Acid anhydride hydrolases}} {{Enzymes}} {{Portal bar|Biology|border=no}}
Category:Cellular processes Category:EC 3.6.5