c-Abl, Lamellipodin, and Ena/VASP Proteins Cooperate in Dorsal Ruffling of Fibroblasts and Axonal Morphogenesis

Michael, Magdalene, Vehlow, Anne, Navarro, Christel and Krause, Matthias (2010) c-Abl, Lamellipodin, and Ena/VASP Proteins Cooperate in Dorsal Ruffling of Fibroblasts and Axonal Morphogenesis. Current Biology, 20 9: 783-791. doi:10.1016/j.cub.2010.03.048


Author Michael, Magdalene
Vehlow, Anne
Navarro, Christel
Krause, Matthias
Title c-Abl, Lamellipodin, and Ena/VASP Proteins Cooperate in Dorsal Ruffling of Fibroblasts and Axonal Morphogenesis
Journal name Current Biology   Check publisher's open access policy
ISSN 0960-9822
1879-0445
Publication date 2010-05-01
Sub-type Article (original research)
DOI 10.1016/j.cub.2010.03.048
Open Access Status DOI
Volume 20
Issue 9
Start page 783
End page 791
Total pages 9
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
Background: Tight regulation of cell motility is essential for many physiological processes, such as formation of a functional nervous system and wound healing. Drosophila Abl negatively regulates the actin cytoskeleton effector protein Ena during neuronal development in flies, and it has been postulated that this may occur through an unknown intermediary. Lamellipodin (Lpd) regulates cell motility and recruits Ena/VASP proteins (Ena, Mena, VASP, EVL) to the leading edge of cells. However, the regulation of this recruitment has remained unsolved. Results: Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins. Consistently, efficient recruitment of Mena and EVL to Lpd at the leading edge requires Abl kinases. Furthermore, transient Lpd phosphorylation by Abl kinases upon netrin-1 stimulation of primary cortical neurons positively correlates with an increase in Lpd-Mena coprecipitation. Lpd is also transiently phosphorylated by Abl kinases upon platelet-derived growth factor (PDGF) stimulation, regulates PDGF-induced dorsal ruffling of fibroblasts and axonal morphogenesis, and cooperates with c-Abl in an Ena/VASP-dependent manner. Conclusions: Our findings suggest that Abl kinases positively regulate Lpd-Ena/VASP interaction, Ena/VASP recruitment to Lpd at the leading edge, and Lpd-Ena/VASP function in axonal morphogenesis and in PDGF-induced dorsal ruffling. Our data do not support the suggested negative regulatory role of Abl for Ena. Instead, we propose that Lpd is the hitherto unknown intermediary between Abl and Ena/VASP
Keyword Tyrosine Kinase
Cell-migration
Actin Cytoskeleton
Family Kinases
Nervous-system
In-Vivo
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 21 Feb 2012, 00:57:52 EST by Susan Allen on behalf of Institute for Molecular Bioscience