Dynamin

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Dynamin family
PDB 2aka EBI.jpg
Structure of the nucleotide-free myosin II motor domain from Dictyostelium discoideum fused to the GTPase domain of dynamin I from Rattus norvegicus
Identifiers
SymbolDynamin_N
PfamPF00350
Pfam clanCL0023
InterProIPR001401
PROSITEPDOC00362
Dynamin central region
PDB 2aka EBI.jpg
Structure of the nucleotide-free myosin II motor domain from Dictyostelium discoideum fused to the GTPase domain of dynamin I from Rattus norvegicus
Identifiers
SymbolDynamin_M
PfamPF01031
InterProIPR000375

Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA, 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.[1][2][3] Dynamin family members also play a role in many processes including division of organelles,[4] cytokinesis and microbial pathogen resistance.

Structure[edit]

Dynamin assembled into helical polymers as visualized by negative stain electron microscopy.[5]

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.[3][6] 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 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[edit]

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. [7][8] 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. [8] Constriction around the vesicle neck leads to the formation of a hemi-fusion membrane state that ultimately results in membrane fission, pinching off the vesicle from the parent membrane. [2][6][9] 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. [10]

Types[edit]

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:

Disease implications[edit]

Mutations in Dynamin II have been found to cause dominant intermediate Charcot-Marie-Tooth disease.[11] Epileptic encephalopathy–causing de novo mutations in dynamin have been suggested to cause dysfunction of vesicle scission during synaptic vesicle endocytosis.[12]

References[edit]

  1. ^ a b Henley JR, Cao H, McNiven MA (December 1999). "Participation of dynamin in the biogenesis of cytoplasmic vesicles". FASEB Journal. 13 Suppl 2 (9002): S243–7. doi:10.1096/fasebj.13.9002.S243. PMID 10619136.
  2. ^ a b Hinshaw, J. "Research statement, Jenny E. Hinshaw, Ph.D." National Institute of Diabetes & Digestive & Kidney Diseases, Laboratory of Cell Biochemistry and Biology. Accessed 19 March 2013.
  3. ^ a b Urrutia R, Henley JR, Cook T, McNiven MA (January 1997). "The dynamins: redundant or distinct functions for an expanding family of related GTPases?". Proceedings of the National Academy of Sciences of the United States of America. 94 (2): 377–84. doi:10.1073/pnas.94.2.377. PMC 34135. PMID 9012790.
  4. ^ Thoms S, Erdmann R (October 2005). "Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation". The FEBS Journal. 272 (20): 5169–81. doi:10.1111/j.1742-4658.2005.04939.x. PMID 16218949.
  5. ^ Hinshaw JE, Schmid SL (March 1995). "Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding". Nature. 374 (6518): 190–2. doi:10.1038/374190a0. PMID 7877694.
  6. ^ a b c Praefcke GJ, McMahon HT (February 2004). "The dynamin superfamily: universal membrane tubulation and fission molecules?". Nature Reviews. Molecular Cell Biology. 5 (2): 133–47. doi:10.1038/nrm1313. PMID 15040446. Lay summaryDynamin Home Page.
  7. ^ Sundborger AC, Fang S, Heymann JA, Ray P, Chappie JS, Hinshaw JE (August 2014). "A dynamin mutant defines a superconstricted prefission state". Cell Reports. 8 (3): 734–42. doi:10.1016/j.celrep.2014.06.054. PMC 4142656. PMID 25088425.
  8. ^ a b Kong L, Sochacki KA, Wang H, Fang S, Canagarajah B, Kehr AD, Rice WJ, Strub MP, Taraska JW, Hinshaw JE (August 2018). "Cryo-EM of the dynamin polymer assembled on lipid membrane". Nature. 560 (7717): 258–262. doi:10.1038/s41586-018-0378-6. PMID 30069048.
  9. ^ Mattila JP, Shnyrova AV, Sundborger AC, Hortelano ER, Fuhrmans M, Neumann S, Müller M, Hinshaw JE, Schmid SL, Frolov VA (August 2015). "A hemi-fission intermediate links two mechanistically distinct stages of membrane fission". Nature. 524 (7563): 109–113. doi:10.1038/nature14509. PMC 4529379. PMID 26123023.
  10. ^ Roux A, Uyhazi K, Frost A, De Camilli P (May 2006). "GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission". Nature. 441 (7092): 528–31. doi:10.1038/nature04718. PMID 16648839.
  11. ^ Züchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, et al. (March 2005). "Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease". Nature Genetics. 37 (3): 289–94. doi:10.1038/ng1514. PMID 15731758.
  12. ^ Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, Johnson MR, Frankel WN, Petrou S, Boumil RM, Goldstein DB (June 2015). "Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis". Neurology. Genetics. 1 (1): e4. doi:10.1212/01.NXG.0000464295.65736.da. PMID 27066543.

External links[edit]