Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1

Abstract

The tumor suppressor protein adenomatous polyposis coli (APC) regulates cell protrusion and cell migration, processes that require the coordinated regulation of actin and microtubule dynamics. APC localizes in vivo to microtubule plus ends and actinrich cortical protrusions, and has welldocumented direct effects on microtubule dynamics. However, its potential effects on actin dynamics have remained elusive. Here, we show that the Cterminal "basic" domain of APC (APCB) potently nucleates the formation of actin filaments in vitro and stimulates actin assembly in cells. Nucleation is achieved by a mechanism involving APCB dimerization and recruitment of multiple actin monomers. Further, APCB nucleation activity is synergistic with its in vivo binding partner, the formin mDia1. Together, APCB and mDia1 overcome a dual cellular barrier to actin assembly imposed by profilin and capping protein. These observations define a new function for APC and support an emerging view of collaboration between distinct actin assembly-promoting factors with complementary activities. © 2010 Okada et al.