Regulation of actin dynamics by Twinfilin

Abstract

Twinfilin is an evolutionarily conserved actin-binding protein initially mischaracterized as a tyrosine kinase but later recognized as a key regulator of cellular actin dynamics. As a member of the ADF-H family, twinfilin binds both actin monomers and filaments. Its role in sequestering G-actin is well-established, but its effects on actin filaments have been debated. While early studies suggested twinfilin caps filament barbed ends, later research demonstrated its role in nucleotide-specific barbed-end depolymerization. Further, it was initially thought to be a processive depolymerase. Recent structural and single-molecule studies have however challenged this view, indicating that twinfilin binding events result in the removal of only one or two actin subunits from the barbed end. Additionally, twinfilin directly binds capping protein (CP) and facilitates uncapping of CP-bound barbed ends. Here, we summarize twinfilin's cellular and tissue-specific localization, and examine its evolving role in regulating cellular actin dynamics in light of its known biochemical functions.