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Int. J. Mol. Sci. 2018, 19(2), 384; https://doi.org/10.3390/ijms19020384

VEGF Triggers the Activation of Cofilin and the Arp2/3 Complex within the Growth Cone

1
Institute of Anatomy, Department of Cytology, Ruhr-University Bochum, Universitätsstraße 150, 44780 Bochum, Germany
2
Research Group Molecular Cardiology, University Hospital Bergmannsheil and St. Josef Hospital, c/o Clinical Pharmacology, Ruhr-University, 44780 Bochum, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 22 December 2017 / Revised: 16 January 2018 / Accepted: 24 January 2018 / Published: 27 January 2018
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Abstract

A crucial neuronal structure for the development and regeneration of neuronal networks is the axonal growth cone. Affected by different guidance cues, it grows in a predetermined direction to reach its final destination. One of those cues is the vascular endothelial growth factor (VEGF), which was identified as a positive effector for growth cone movement. These positive effects are mainly mediated by a reorganization of the actin network. This study shows that VEGF triggers a tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton within chicken dorsal root ganglia (DRG). Live cell imaging after microinjection of GFP (green fluorescent protein)-cofilin and RFP (red fluorescent protein)-LifeAct revealed that both labeled proteins rapidly redistributed within growth cones, and showed a congruent distribution pattern after VEGF supplementation. Disruption of signaling upstream of cofilin via blocking LIM-kinase (LIMK) activity resulted in growth cones displaying regressive growth behavior. Microinjection of GFP-p16b (a subunit of the Arp2/3 complex) and RFP-LifeAct revealed that both proteins redistributed into lamellipodia of the growth cone within minutes after VEGF stimulation. Disruption of the signaling to the Arp2/3 complex in the presence of VEGF by inhibition of N-WASP (neuronal Wiskott–Aldrich–Scott protein) caused retraction of growth cones. Hence, cofilin and the Arp2/3 complex appear to be downstream effector proteins of VEGF signaling to the actin cytoskeleton of DRG growth cones. Our data suggest that VEGF simultaneously affects different pathways for signaling to the actin cytoskeleton, since activation of cofilin occurs via inhibition of LIMK, whereas activation of Arp2/3 is achieved by stimulation of N-WASP. View Full-Text
Keywords: VEGF; cofilin; Arp2/3; LIMK; N-WASP; time-lapse imaging; growth cone; cytoskeleton; actin VEGF; cofilin; Arp2/3; LIMK; N-WASP; time-lapse imaging; growth cone; cytoskeleton; actin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Schlau, M.; Terheyden-Keighley, D.; Theis, V.; Mannherz, H.G.; Theiss, C. VEGF Triggers the Activation of Cofilin and the Arp2/3 Complex within the Growth Cone. Int. J. Mol. Sci. 2018, 19, 384.

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