Dynamin

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Dynamin proteins assembled into spirals.
Dynamin
Identifiers
Symbol DNM1 DNM2 DNM3
HUGO {{{HGNCid}}}
Entrez 1759
OMIM 602377
UniProt Q05193
Other data
EC number 3.6.1.50
Locus Chr. 9 q34

Dynamin is a GTPase thought to be 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[1][2][3] Dynamin also plays a role in many processes including division of organelles, cytokinesis and microbial pathogen resistance.

Dynamin is part of a ‘’Dynamin Superfamily’’ that includes classical dynamins, dynamin-like proteins, Mx proteins, OPA, mitofusins, and GBPs. Dynamin itself is a 100 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.[4][3]

Contents

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 (when guanosine triphosphate is converted to guanosine diphosphate). 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.[2][4]

To view the effect of GTP and GDP on dynamin spirals, please follow this link: http://dynamin.niddk.nih.gov/figure2.html. [2] In part A of this picture we see dynamin tubes while they are in the presence of GTP; they are large and relaxed. In part B of the picture we see the same dynamin tubes from part one, but in the presence of GDP; they are tight. 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.jpg.[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.

To see a cartoon image of the way dynamin is thought to work within the cell, please follow this link.[1]

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, and Dynamin III is strongly expressed in the testis, but is also present in heart, brain, and lung tissue.[1][4]

Two recent findings suggest that reducing endocytosis of synaptic vesicles by inhibiting dynamin may be a useful treatment for epilepsy. Small molecule inhibitors of dynamin are currently being tested for their anti-epileptic effect.[5]

It has also been suggested that the mechanism of action for Ketogenic Diet as a treatment for epilepsy is via reducing synaptic GTP concentrations and reducing dynamin-dependent endocytosis.[6]

  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, Vol. 94, 377-384.
  4. ^ a b c McMahon. (2004). “Researching Endocytic Mechanisms: Dynamin:. Accompaniment of Nature Reviews on Molecular Cell Biology, 5, 133-147.
  5. ^ http://www.biolink.org.au/library/File/Bio-Link%20-%20Dynamin%20Inhibitor%20Summary%20-%20Epilepsy%20-%20121406.pdf
  6. ^ http://pepck-and-the-ketogenic-diet.com/GTPsynaptictransmission.html

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