Dynamin

Dynamin_N
structure of the nucleotide-free myosin ii motor domain from dictyostelium discoideum fused to the gtpase domain of dynamin 1 from rattus norvegicus
Identifiers
Symbol	Dynamin_N
Pfam	PF00350
Pfam clan	CL0023
InterPro	IPR001401
PROSITE	PDOC00362
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

Dynamin central region
structure of the nucleotide-free myosin ii motor domain from dictyostelium discoideum fused to the gtpase domain of dynamin 1 from rattus norvegicus
Identifiers
Symbol	Dynamin_M
Pfam	PF01031
InterPro	IPR000375
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins 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 also plays a role in many processes including division of organelles,^[4] cytokinesis and microbial pathogen resistance.

Dynamin is part of the "Dynamin Superfamily," which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA, mitofusins, and GBPs. 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 within clathrin-coated vesicle budding from the cell membrane.^[3][5]

Function

As a vesicle invaginates, dynamin forms a spiral around the neck of the vesicle. Once the spiral is in place, it extends lengthwise and constricts through GTP hydrolysis. This lengthening and tightening of the coil around the vesicle neck causes it to break and results in the pinching off of the vesicle from the parent membrane. An example of a vesicle is a clathrin-coated pit.^[2][5]

To view the effect of GTP and GDP on dynamin spirals, follow this link: http://dynamin.niddk.nih.gov/figure2.html.^[2] In part A of this picture we see dynamin tubes in the absence of GTP; they are large and relaxed. In part B of the picture we see the same dynamin tubes from part one but after addition of GTP, GTP is hydrolysed because of intrinsic GTPase activity and constriction ensues. This is how dynamin works to pinch vesicles off from the membrane.

To view a ‘cartoon’ image of the non-constricted and constricted state of dynamin spirals, please follow this link: http://dynamin.niddk.nih.gov/figure5.html.^[2] The first structure on the left is dynamin in its relaxed state. The structure on the right is dynamin in its constricted state. This allows you to see how much dynamin tightens and changes when GTP is converted to GDP.^[1]

This constriction is in part the result of the twisting activity of dynamin ^[6] This twisting is strictly dependent on its GTPase activity. Dynamin is the only molecular motor known to have a twisting activity. Dynamin is a right-handed helix, and has a right-handed twisting activity that explains its tightening and the pitch reduction described above.

Types

In mammals, three different dynamin genes have been identified.

• Dynamin II is expressed in most cell types;
• Dynamin I is expressed in neurons and neuroendocrine cells
• Dynamin III is strongly expressed in the testis, but is also present in heart, brain, and lung tissue.^[1][5]

Disease implications

Mutations in Dynamin II have been found to cause dominant intermediate Charcot-Marie-Tooth disease.^[7]

References

1. ^ ^{a b c} Henley, J.R., Cao, H., McNicven, M.A. (1999). “Participation of dynamin in the biogenesis of cytoplasmic vesicles”. The FASEB Journal, 13, S243-S247.
2. ^ ^{a b c d} Hinshaw, J. “Dynamin overview: The Role of Dynamin in Membrane Fission”. National institute of diabetes & digestive & kidney diseases, Laboratory of cell biochemistry and biology. accessed 021806.
3. ^ ^{a b} Urrutia, R.; Henley, J.R.; Cook, T.; McNiven, M.A. (1997). "The dynamins: Redundant or distinct functions for an expanding family of related GTPases?". Proc. Natl Acad. Sci. USA 94 (2): 377–384. doi:10.1073/pnas.94.2.377. http://www.pnas.org/cgi/content/full/94/2/377?ijkey=cc76b66f40ce6a1c4bef3246109754c5ca3cc425. 
4. ^ Thoms S, Erdmann R (Oct 2005). "Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation.". FEBS J 272 (20): 5169–81. doi:10.1111/j.1742-4658.2005.04939.x. PMID 16218949. 
5. ^ ^{a b c} McMahon. (2004). “Researching Endocytic Mechanisms: Dynamin:. Accompaniment of Nature Reviews on Molecular Cell Biology, 5, 133-147.
6. ^ Roux, A; Uyhazi, K; Frost, A; De Camilli, P (2006-04-30). "GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission". Nature a - z index 441 (7092): 528–31. doi:10.1038/nature04718. PMID 16648839. http://www.nature.com/nature/journal/v441/n7092/abs/nature04718.html;jsessionid=B2DCD26EE59C1918B5A66ECA9542A843. 
7. ^ Stephan Zuchner, Maher Noureddine, Marina Kennerson, Kristien Verhoeven, Kristl Claeys, Peter De Jonghe, John Merory, Sofia A. Oliveira, Marcy C. Speer, Judith E. Stenger, Gina Walizada, Danqing Zhu, Margaret A. Pericak-Vance, Garth Nicholson, Vincent Timmerman & Jeffery M. Vance (March 2005). "Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease". Nature genetics 37 (3): 289–294. doi:10.1038/ng1514. PMID 15731758. 

External links

• MeSH Dynamins