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First published online April 24, 2006
doi: 10.1242/10.1242/jcs.02963

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Dynamin as a mover and pincher during cell migration and invasion

Center for Basic Research in Digestive Diseases and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA

View larger version (132K): [in a new window]   Fig. 1. Dynamin self-assembles and tubulates lipids. (A) Scheme of dynamin protein showing the GTPase domain, the middle domain (MID), the pleckstrin-homology domain (PH), the GED domain, and the proline-rich domain (PRD). (B) Negative stain showing that dynamin protein self-assembles into rings in the presence of GTPS; adapted from Hinshaw (Hinshaw, 2000), reprinted with permission. (C) The surface rendering depicts dynamin's ability to constrict around tubules in an ordered manner. The dynamin head domain is shown in green, the stalk is blue, the leg is gold, and the inner lipid leaflet is grey; adapted from Zhang and Hinshaw (Zhang and Hinshaw, 2001), reprinted with permission. Cryo-EM of PRD tubules before (D) and 5 seconds after (E) addition of GTP. The diagrams below each panel depict the constriction of the tubules in the presence of GTP. White arrows indicate undecorated lipid bulges and black arrowheads indicate transitions between constricted, decorated tubules and lipid bulges; adapted from Danino et al. (Danino et al., 2004), reprinted with permission. Bar, 100 nm. Negative stain of GDP-AlF (F) and GDP (G) dynamin on tubules depicting the change in pitch of dynamin rings after hydrolysis of GTP occurs; adapted from Stowell et al. (Stowell et al., 1999), reprinted with permission.

View larger version (148K): [in a new window]   Fig. 2. Dynamin tubulates lipids cooperatively with the actin cytoskeleton. (A,B) Co-expression of RFP-FBP17, an F-BAR-domain-containing protein, and GFP-Dyn2 results in antagonization of formation of lipid tubules, which is relieved by disruption of the actin cytoskeleton by Latrunculin B treatment (B). (A') and (B') provide a higher magnification of the vesiculation (A') or tubulation (B') of lipids at the plasma membrane. These data demonstrate the importance of the cooperation of Dyn2 and actin in vesiculation of the membrane; adapted from Itoh et al. (Itoh et al., 2005), reprinted with permission. (C) Fluorescence image of a rat fibroblast expressing a GFP-Dyn2abK44A mutant, which results in formation of dynamin-coated lipid tubules extending inwards from the plasma membrane (Cao, H. and M.A.M., unpublished data). (D,E) Two examples of PIP2-containing membranes developing long actin cables in the presence of GTP. Long actin filament bundles form, demonstrating dynamin's ability to alter the organization of actin filaments; adapted from Schafer et al. (Schafer et al., 2002), reprinted with permission.

View larger version (108K): [in a new window]   Fig. 3. Dynamin participates in dorsal wave and lamellipodia formation. (A) Fluorescence image of a dorsal wave in a rat fibroblast stimulated for 5 minutes with PDGF that accumulates both Dyn2 (green) and actin (red) at the progressing wave structure (Orth, J. D. and M.A.M., unpublished data). (B) Dyn2 and cortactin accumulate at the leading edge of a rat fibroblast stimulated with EGF (Orth, J. D. and M.A.M., unpublished data). (C) Wild-type dynamin and Rac accumulate in the lamellipodium of an NIH3T3 fibroblast co-expressing constitutively active Rac, whereas dominant-negative Dyn2K44A (D) disrupts lamellipodial extension as well as accumulation of Rac at the lamellipodium. Confocal imaging was used to create Z-series reconstructions, indicated by the lines in (C) and (D) and shown in (C') and (D'); adapted from Schlunck et al. (Schlunck et al., 2004), reprinted with permission.

View larger version (139K): [in a new window]   Fig. 4. Dynamin localizes to focal adhesions, podosomes and invadopodia. Dynamin (A) colocalizes with constitutively active SrcY530F (B) in HeLa cells at the sites of focal adhesions (C, merge) (Cao, H. and M.A.M., unpublished data). Osteoclasts form a podosome ring, which accumulates both actin (D) and Dyn2 (E). (F) Confocal imaging shows the overlap of Dyn2 (green) and actin (red) at high resolution. A375MM melanoma cells demonstrate an association of Dyn2 (I) with actin (H) at invadopodia where the degradation of extracellular matrix occurs (G, arrows); adapted from Baldassarre et al. (Baldassarre et al., 2003), reprinted with permission.

View larger version (37K): [in a new window]   Fig. 5. Dynamin regulates multiple aspects of cell migration. Through its action as a polymeric scaffold protein and a GTPase, Dyn2 localizes to focal adhesions, invadopodia, podosomes, dorsal waves, and lamellipodia to promote cell migration.

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