Conserved tyrosine Y16 acts as a phosphorylation switch controlling Ena/VASP recruitment to sites of actin assembly

Phosphorylation of Y16 in vertebrate Ena/VASP proteins is the decisive inhibitory modification that controls subcellular Ena/VASP recruitment, unlike proposed roles for Y39 and S157.

• Why it matters: Ena/VASP proteins accumulate at active actin assembly sites, but how their recruitment is regulated by phosphorylation has remained unclear, limiting understanding of adhesion, migration, and pathogenesis control.
• What they did: In cells lacking all Ena/VASP-family members, the authors reconstituted phosphomimetic and nonphosphorylatable substitutions at conserved tyrosine/serine residues and used cell-based reconstitution plus biochemical assays to test targeting.
• The result: Phosphomimetic substitutions in the C. elegans orthologue UNC-34 phenocopied uncoordinated locomotion of UNC-34 null worms, supporting evolutionary conservation of the Y16 phosphorylation-sensitive recruitment switch.