Biology subjects

Wu, S.-y.

Publications and source records attributed to Wu, S.-y..

3 recordsLinked to original sources

bioRxiv2025

The Actin regulator Mena promotes Wnt signalosome endocytosis and Wnt signalling.

Wnt signaling controls embryonic development and tissue maintenance. Endocytosis of Wnt-receptors is required for signalling, yet uptake mechanisms remain poorly understood. Here, we identify the actin regulator and Ena/VASP protein, Mena, as a key mediator. Upon Wnt stimulation, Mena redistributes from focal adhesions to signalosomes, Wnt-receptor clusters. Mena directly binds Wnt-coreceptors LRP5/6 in a phosphorylation-dependent manner increasing Wnt signal transduction. Sequestration of Ena/VASP proteins impedes in vivo Wnt activation driving Xenopus embryonic development. We resolve previous controversies by showing that Wnt3a triggers rapid Clathrin-Mediated and Fast Endophilin-Mediated LRP6 endocytosis at low concentrations sufficient for Wnt activation. This efficient endocytosis requires Ena/VASP proteins and is specifically promoted by Mena. Our results suggest Mena as a crucial mediator of Wnt signalosome endocytosis thus promoting canonical Wnt signalling.

cell biology↗

bioRxiv2025

The NHSL1-A complex interacts with the Arp2/3 complex and controls cell migration efficiency and chemotaxis.

Cell migration is crucial for development and deregulation causes diseases. The Scar/WAVE complex promotes mesenchymal cell migration through Arp2/3 mediated lamellipodia protrusion. We previously discovered that all isoforms of Nance-Horan Syndrome-like 1 (NHSL1) protein interact directly with the Scar/WAVE complex and the NHSL1-F1 isoform negatively regulates Scar/WAVE-Arp2/3 activity thereby inhibiting 2D random cell migration. Here, we investigate the NHSL1-A1 isoform, which contains a Scar homology domain (SHD). The SHD in Scar/WAVE mediates the formation of the Scar/WAVE complex. We found that the SHD of NHLS1-A is sufficient for the formation of an NHSL1-A complex composed of the same proteins as the Scar/WAVE complex, but NHSL1-A replaces Scar/WAVE. NHSL1-A SHD recruits the NHSL1-A complex to lamellipodia, where also the Scar/WAVE complex resides. Scar/WAVE contains a WCA domain, which is phosphorylated by CK2 and recruits and activates the Arp2/3 complex to nucleate branched actin networks supporting lamellipodial protrusion. We identified a WCA domain in NHSL1 which interacts with the Arp2/3 complex. The NHSL1 WCA domain is phosphorylated by GSK3, and this increases the interaction with the Arp2/3 complex. In contrast to NHSL1-F1, the NHSL1-A complex promotes cell migration speed but not cell persistence via the Scar/WAVE complex and potentially via its WCA domain. In addition, the NHSL1-A complex is required for chemotaxis. Mechanistically, the NHSL1-A complex may increase lamellipodial Arp2/3 activity and lamellipodial speed while reducing lamellipodial persistence. Our findings reveal an additional layer of Arp2/3 complex control essential for mesenchymal cell migration highly relevant for development and disease.

cell biology↗

bioRxiv2022

GSK3 and Lamellipodin balance lamellipodial protrusions and focal adhesion maturation in mouse neural crest migration

Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating to distant destinations throughout the embryo. Aberrant migration has severe consequences, such as congenital disorders. While animal models have improved our understanding of neural crest anomalies, the in vivo contributions of actin-based protrusions are still poorly understood. Here, we demonstrate that murine neural crest cells use lamellipodia and filopodia in vivo. Using neural crest-specific knockouts or inhibitors, we show that the serine-threonine kinase, Glycogen Synthase Kinase-3 (GSK3), and the cytoskeletal regulator, Lamellipodin (Lpd), are required for lamellipodia formation whilst preventing focal adhesion maturation. We consequently identified Lpd as a novel substrate of GSK3 and found that phosphorylation of Lpd favours Lpd interactions with the Scar/WAVE complex (lamellipodia formation) at the expense of Ena/VASP protein interactions (adhesion maturation and filopodia formation). All together, we provide an improved understanding of cytoskeletal regulation in mammalian neural crest migration, which has general implications for neural crest anomalies and cancer. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/521694v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1ef8e9eorg.highwire.dtl.DTLVardef@7c3a87org.highwire.dtl.DTLVardef@1e67e8corg.highwire.dtl.DTLVardef@17e269c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗