Involvement of actin polymerization in podosome dynamics

Abstract

Podosomes, formed by different monocyte derivatives, are small adhesion structures whose coordinated dynamics and cytoskeletal reorganization drive their motile and invasive features. Using live-cell microscopy, we explored the temporal molecular steps of the de novo assembly and disassembly of podosomes in cultured osteoclasts. We demonstrate here that the earliest visible step in podosome assembly is the local accumulation of the plaque protein paxillin, along with cortactin, which stabilizes actin networks, followed by robust polymerization of actin filaments, and their association with α-actinin. Only then, a local increase in integrin β3 levels is apparent in the podosome ring domain. Thus, local actin polymerization in paxillin-rich locations nucleates podosome assembly prior to the local accumulation of β3 integrin. We further show that actin polymerization is also critical for the recruitment and maintenance of plaque proteins in the mature podosome ring domain. Our model implies that core bundle dynamics play a central role in regulating podosome stability.