A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells.
The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These "waves" promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.
Krueger
Eugene W
EW
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Orth
James D
JD
Cao
Hong
H
McNiven
Mark A
MA
D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D051356:Cortactin; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
C495928:ACTR3 protein, human; D051378:Actin-Related Protein 3; D000199:Actins; C495929:Actr3 protein, mouse; C495868:CTTN protein, human; D051356:Cortactin; C495869:Cttn protein, mouse; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D034281:Dynamins