Mammalian clathrin light chains (CLCa, CLCb) are critical players in clathrin-mediated endocytosis. However, their physiological role in contributing to specific cellular processes and early development remains elusive. To elucidate their individual functions, we generated CLC knockout mESCs. Loss of CLCa resulted in down-regulation of Wnt pathway genes along with altered secretion of Wnt3a because of impaired trafficking of its secretion mediator, WLS. Reduced Wnt signaling led to lower levels of Hip1R causing a reorganization of the actin cytoskeleton. CLCa knockout cells displayed actin patches enriched for Arp3 and cortactin, with activation of the Wnt pathway resulting in disassembly of these patches. Furthermore, we uncovered a bidirectional cross-talk between Wnt signaling and actin organization, with actin disruption resulting in lower Wnt signaling. Our data reveal a previously undiscovered role of CLCa in mediating molecular communication between actin organization and Wnt signaling.
© 2025 Tiwari et al.
