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Actin branching: Coronin 1B vs. cortactin

Cell Migration Gateway (October 2008) | doi:10.1038/cmg079

Coronin 1B antagonizes the actin branch stabilizing activity of cortactin by inducing the dissociation of the actin-related protein-2/3 (ARP2/3) complex from actin branches, thus regulating actin dynamics at the lamellipodia.

Actin branches from negative staining EM. Images show a mixture of ARP2/3- and Coronin 1B-containing branches.

Image courtesy of Dr James E. Bear, University of North Carolina at Chapel Hill, USA.

The actin-related protein-2/3 (ARP2/3) complex catalyses actin nucleation at the sides of existing filaments and remains localised at branch junctions to stabilize the resulting F-actin network. Although branched filament assembly is well characterised, the mechanisms underlying network disassembly remain poorly understood. Reporting in Cell, James Bear and colleagues now show that the actin-binding protein coronin 1B disassembles actin branches by inducing dissociation of the ARP2/3 complex.

Coronin 1B has previously been shown to inhibit actin nucleation through the ARP2/3 complex, but the details of this inhibitory function are not known. The authors first analysed coronin 1B localization relative to that of cortactin — a known ARP2/3-containing branch stabiliser. Localisation of both proteins partially overlapped at the lamellipodia, although with different distributions. Coronin 1B and cortactin were also found to bind different pools of ARP2/3 complex, which prompted the authors to investigate whether these two proteins were able to functionally interact. Depletion of either coronin 1B or cortactin in mouse fibroblasts impaired cell protrusion. However, loss of both proteins partially restored cell protrusion dynamics, suggesting that coronin 1B and cortactin might have an antagonistic effect on actin dynamics.

In agreement with this result, coronin 1B strongly inhibited cortactin-mediated actin nucleation in vitro. When the authors monitored actin polymerization branching they discovered that rather than affecting the rate of filament elongation, coronin 1B reduced both the density and the stability of the actin branches — an effect that was reversed levels of cortactin were increased. Furthermore, the authors found that the amounts of ARP2/3 complex associated with F-actin were reduced in the presence of coronin 1B, showing that coronin 1B induces the dissociation of the ARP2/3 complex from the sides of actin filaments.

Although there is a considerable overlap in the localisation of coronin 1B and cortactin they occupy different regions in the lamellipodia. The authors found that cortactin co-localises with the ARP2/3 complex close to the leading edge whereas coronin 1B tends to accumulate more deeply in the lamellipodia — in areas with gradually reduced levels of ARP2/3 complex. This finding, together with the observation that coronin 1B and the ARP2/3 complex are mutually exclusive at branches in vitro, suggests that coronin 1B targets pre-existing ARP2/3-containing branches and replaces the ARP2/3 complex.

Expression of a membrane-targeted coronin 1B mutant reduced ARP2/3 complex branch density and affected protrusion dynamics at the leading edge — protrusion rate was increased and protrusion persistence decreased. Furthermore, depletion of coronin 1B or cortactin disrupted the normal actin and ARP2/3 complex retrograde flow in lamellipodia.

These findings highlight the importance of regulating the spatial and temporal distribution of coronin 1B at the leading edge to ensure proper actin dynamics. The authors propose that following F-actin branch formation by the ARP2/3 complex, coronin 1B targets to ARP2/3-containing branches where it antagonises the stabilising function of cortactin. This leads to dissociation of the ARP2/3 complex leaving coronin 1B on the branch, which in turn might trigger subsequent steps required for filament turnover.

Kim Baumann - Copyright © 2008 Nature Publishing Group, a division of MacMillan Publishers Limited; used with permission

Original Research Article

  1. Cai , L. , Makhov , A. M. , Schafer , D. A. & Bear , J. E. Coronin 1B Antagonizes Cortactin and Remodels Arp2/3-Containing Actin Branches in Lamellipodia. Cell 134, 828–842 (2008).
    doi: 10.1016/j.cell.2008.06.054