Profilin-1 Controls Actin Network Organization And Homeostasis Through Coordination With Other Assembly Factors
BIOPHYSICAL JOURNAL(2020)
Abstract
Cells use a variety of actin binding proteins to regulate every aspect of actin assembly but the rules that determine how complex networks form from multiple assembly factors remain poorly understood. Profilin-1 (PFN1) buffers the actin monomer pool and promotes polymerization through interactions with polymerases, allowing it to bias assembly of specific types of actin networks. In this study, we sought to understand how PFN1 controls actin assembly, organization, and homeostasis in the elaborate environment of mammalian cells where multiple assembly factors are operating simultaneously and dynamically in a common cytoplasm. In PFN1 knock-out (KO) cells, the ability to polymerize actin through Arp2/3 and formins is partially lost, while assembly by Mena/VASP is completely inhibited. We also found PFN1 is necessary to maintain monomer/filament homeostasis, even when Arp2/3 or formins are inhibited. PFN1 KO cells also have depleted lamellipodia actin and a loss of Arp2/3 localization to the leading edge. By reintroducing discrete amounts of PFN1 protein, we identified a concentration-dependent relationship of PFN1 to lamellipodia architecture. Lower profilin concentrations stimulate the formation of filipodia and linear filament arrays and allow Arp2/3 to re-localize to the leading edge, while higher concentrations stimulate dendritic network assembly. These findings demonstrate a nuanced, coordinate action of PFN1 with other actin binding proteins and suggest that filaments generated through PFN1 create the majority of Arp2/3 binding sites.
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Key words
actin,homeostasis
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