The conformational state of actin filaments regulates branching by actin-related protein 2/3 (Arp2/3) complex
Journal Article

Published: Friday, September 07, 2012
Journal: Journal of Biological Chemistry, Volume 287, Number 37, Pages 31447-31453
Link: http://www.jbc.org/content/287/37/31447

Authors (1 total): M. H. Jensen

Abstract:

Actin is a highly ubiquitous protein in eukaryotic cells which plays a crucial role in cell mechanics and motility. Cell motility is driven by assembling actin, as polymerizing actin drives cell protrusions in a process closely involving a host of other actin-binding proteins, notably the actin-related protein 2/3 (Arp2/3) complex, which nucleates actin and forms branched filamentous structures. The Arp2/3 complex preferentially binds specific actin networks at the cell leading edge and forms branched filamentous structures, which drive cell protrusions, but the exact regulatory mechanism behind this process is not well understood. Here we show using in vitro imaging and binding assays that a fragment of the actin-binding protein caldesmon added to polymerizing actin increases the Arp2/3-mediated branching activity, while it has no effect on branch formation when binding to aged actin filaments. Since this caldesmon effect is shown to be independent of nucleotide hydrolysis and phosphate release from actin, our results suggest a mechanism by which caldesmon maintains newly polymerized actin in a distinct state that has a higher affinity for the Arp2/3 complex. Our data show that this new state does not affect the level of cooperativity of binding by Arp2/3 complex or its distribution on actin. This presents a novel regulatory mechanism by which caldesmon, and potentially other actin binding proteins, regulate the interactions of actin with its binding partners.