Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin

S. Koestler, A. Steffen, M. Nemethova, M. Winterhoff, N. Luo, J. Holleboom, J. Krupp, S. Jacob, M. Vinzenz, F. Schur, K. Schlüter, P. Gunning, C. Winkler, C. Schmeiser, J. Faix, T. Stradal, J. Small, K. Rottner, Molecular Biology of the Cell 24 (2013) 2861–2875.

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Abstract
Lamellipodia are sheet-like protrusions formed during migration or phagocytosis and comprise a network of actin filaments. Filament formation in this network is initiated by nucleation/branching through the actin-related protein 2/3 (Arp2/3) complex downstream of its activator, suppressor of cAMP receptor/WASP-family verprolin homologous (Scar/WAVE), but the relative relevance of Arp2/3-mediated branching versus actin filament elongation is unknown. Here we use instantaneous interference with Arp2/3 complex function in live fibroblasts with established lamellipodia. This allows direct examination of both the fate of elongating filaments upon instantaneous suppression of Arp2/3 complex activity and the consequences of this treatment on the dynamics of other lamellipodial regulators. We show that Arp2/3 complex is an essential organizer of treadmilling actin filament arrays but has little effect on the net rate of actin filament turnover at the cell periphery. In addition, Arp2/3 complex serves as key upstream factor for the recruitment of modulators of lamellipodia formation such as capping protein or cofilin. Arp2/3 complex is thus decisive for filament organization and geometry within the network not only by generating branches and novel filament ends, but also by directing capping or severing activities to the lamellipodium. Arp2/3 complex is also crucial to lamellipodia-based migration of keratocytes.
Publishing Year
Date Published
2013-09-15
Journal Title
Molecular Biology of the Cell
Acknowledgement
This work was supported in part by Deutsche Forschungsgemeinschaft Grants RO2414/3-1 (to K.R.) and FA330/6-1 (to J.F.), Austrian Science Fund Projects FWF 1516-B09 and FWF P21292-B09 (to J.V.S.), the Vienna Science and Technology Fund (WWTF, to J.V.S. and C.S.), and Australian National Health and Medical Research Council Grant APP1004175 (to P.W.G.). We thank J. Adams, R. Chisholm, A. Hall, L. Machesky, H. G. Mannherz, D. Schafer, and R. Wedlich-Söldner for expression constructs and B. Denker, P. Hagendorff, and G. Landsberg for technical assistance.
Volume
24
Issue
18
Page
2861 - 2875
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Koestler S, Steffen A, Nemethova M, et al. Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin. Molecular Biology of the Cell. 2013;24(18):2861-2875. doi:10.1091/mbc.E12-12-0857
Koestler, S., Steffen, A., Nemethova, M., Winterhoff, M., Luo, N., Holleboom, J., … Rottner, K. (2013). Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin. Molecular Biology of the Cell, 24(18), 2861–2875. https://doi.org/10.1091/mbc.E12-12-0857
Koestler, Stefan, Anika Steffen, Maria Nemethova, Moritz Winterhoff, Ningning Luo, J. Holleboom, Jessica Krupp, et al. “Arp2/3 Complex Is Essential for Actin Network Treadmilling as Well as for Targeting of Capping Protein and Cofilin.” Molecular Biology of the Cell 24, no. 18 (2013): 2861–75. https://doi.org/10.1091/mbc.E12-12-0857.
S. Koestler et al., “Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin,” Molecular Biology of the Cell, vol. 24, no. 18, pp. 2861–2875, 2013.
Koestler S, Steffen A, Nemethova M, Winterhoff M, Luo N, Holleboom J, Krupp J, Jacob S, Vinzenz M, Schur F, Schlüter K, Gunning P, Winkler C, Schmeiser C, Faix J, Stradal T, Small J, Rottner K. 2013. Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin. Molecular Biology of the Cell. 24(18), 2861–2875.
Koestler, Stefan, et al. “Arp2/3 Complex Is Essential for Actin Network Treadmilling as Well as for Targeting of Capping Protein and Cofilin.” Molecular Biology of the Cell, vol. 24, no. 18, American Society for Biology, 2013, pp. 2861–75, doi:10.1091/mbc.E12-12-0857.

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