Twinfilin is a potent uncapper of actin capping protein and modulates actomyosin contractility in the C. elegans spermatheca

The actin cytoskeleton is dynamically remodelled by conserved regulators to control cellular and tissue mechanics. While the functions of these proteins are well studied, how they drive tissue-specific contractility remains unclear. Twinfilin, an actin uncapper and depolymerase, has not previously been linked to tissue contractility. Here, we show that the sole twinfilin ortholog in C. elegans, TWF-2, regulates actomyosin contractility in the spermatheca. TWF-2 localizes to the spermathecal cortex via interactions with -spectrin (SPC-1) and {beta}-spectrin (UNC-70). In vitro, TWF-2 promotes barbed-end depolymerization and rapidly removes CAP-1 from actin filaments. In vivo, embryonic lethality caused by CAP-1 depletion is partially rescued by simultaneous loss of TWF-2. Similarly, loss of the contractility regulator SPV-1 leads to elevated F-actin and phosphorylated myosin, causing hypercontractility. Notably, removing TWF-2 suppresses this hypercontractility by reducing F-actin levels-- without affecting myosin or its phosphorylation--highlighting a specific role in F-actin regulation. Together, these findings show that TWF-2 modulates actin dynamics in a tissue-specific manner. This work provides the first in vivo evidence that twinfilin regulates contractility, and reveals how its interactions with capping protein and spectrins help maintain balanced actomyosin levels in the spermatheca.