Dynamin is aGTPase protein responsible forendocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins,Mx proteins,OPA1,mitofusins, andGBPs. Members of the dynamin family are principally involved in the scission of newly formedvesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (particularlycaveolae internalization) as well as at theGolgi apparatus.[1][2][3] Dynamin family members also play a role in many processes including division oforganelles,[4]cytokinesis and microbialpathogen resistance.
Dynamin assembled into helical polymers as visualized by negative stain electron microscopy.[5]
Dynamin itself is a 96kDaenzyme, and was first isolated when researchers were attempting to isolate newmicrotubule-based motors from the bovine brain. Dynamin has been extensively studied in the context ofclathrin-coated vesicle budding from thecell membrane.[3][6] Beginning from theN-terminus, Dynamin consists of a GTPase domain connected to a helical stalk domain via a flexible neck region containing a Bundle Signalling Element andGTPase Effector Domain. At the opposite end of the stalk domain is a loop that links to a membrane-bindingPleckstrin homology domain. The protein strand then loops back towards the GTPase domain and terminates with aProline Rich Domain that binds to theSrc Homology domains of many proteins.
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 uponGTP 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-fission membrane state that ultimately results in membrane scission.[2][6][9] Constriction may be in part the result of the twisting activity of dynamin, which makes dynamin the onlymolecular motor known to have a twisting activity.[10]
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:
Small molecule inhibitors of dynamin activity have been developed, including Dynasore[11][12] and photoswitchable derivatives (Dynazo)[13] for spatiotemporal control of endocytosis with light (photopharmacology).
Mutations inDynamin II have been found to cause dominant intermediateCharcot-Marie-Tooth disease.[14]Epileptic encephalopathy–causing de novo mutations in dynamin have been suggested to cause dysfunction of vesicle scission during synaptic vesicle endocytosis.[15]
^Thoms S, Erdmann R (October 2005). "Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation".The FEBS Journal.272 (20):5169–5181.doi:10.1111/j.1742-4658.2005.04939.x.PMID16218949.
^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):289–294.doi:10.1038/ng1514.PMID15731758.S2CID19191581.
