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Mol Biol Cell. 2018 Nov 15;29(23):2863-2873. doi: 10.1091/mbc.E18-01-0044. Epub 2018 Sep 26.

Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension.

Author information

1
Department of Cell Biology, Yale University, New Haven, CT 06520.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520.
3
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030.
4
Department of Neuroscience, Yale University, New Haven, CT 06520.

Abstract

Abl family nonreceptor tyrosine kinases regulate changes in cell shape and migration. Abl2 localizes to dynamic actin-rich protrusions, such as lamellipodia in fibroblasts and dendritic spines in neurons. Abl2 interactions with cortactin, an actin filament stabilizer, are crucial for the formation and stability of actin-rich structures, but Abl2:cortactin-positive structures have not been characterized with high spatiotemporal resolution in cells. Using total internal reflection fluorescence microscopy, we demonstrate that Abl2 colocalizes with cortactin at wave-like structures within lamellum and lamellipodium tips. Abl2 and cortactin within waves are focal and transient, extend to the outer edge of lamella, and serve as the base for lamellipodia protrusions. Abl2-positive foci colocalize with integrin β3 and paxillin, adhesive markers of the lamellum-lamellipodium interface. Cortactin-positive waves still form in Abl2 knockout cells, but the lamellipodium size is significantly reduced. This deficiency is restored following Abl2 reexpression. Complementation analyses revealed that the Abl2 C-terminal half, which contains domains that bind actin and microtubules, is necessary and sufficient for recruitment to the wave-like structures and to support normal lamellipodium size, while the kinase domain-containing N-terminal half does not impact lamellipodium size. Together, this work demonstrates that Abl2 is recruited with cortactin to actin waves through cytoskeletal interactions to promote lamellipodium extension.

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