Refilins are short-lived Actin-bundling proteins that regulate lamellipodium protrusion dynamics

Abstract

Refilins (RefilinA and RefilinB) are members of a novel family o Filamin binding proteins that function as molecular switches t conformationally alter the Actin filament network into bundles. W show here that Refilins are extremely labile proteins. An N-Termina PEST/DSG(X)2-4S motif mediates ubiquitin-independent rapi degradation. A second degradation signal is localized within th C-Terminus. Only RefilinB is protected from rapid degradation by a auto-inhibitory domain that masks the PEST/DSG(X)2-4S motif. Dua regulation of RefilinA and RefilinB stability was confirmed in rat brai NG2 precursor cells (polydendrocyte). Using loss-and gain-offunctio approaches we show that in these cells, and in U373M cells, Refilins contribute to the dynamics of lamellipodium protrusio by catalysing Actin bundle formation within the lamella Actin network These studies extend the Actin bundling function of the Refilin Filamin complex to dynamic regulation of cell membrane remodelling.