Angermeier Allyson, Yu Deli, Huang Yali, Marchetto Sylvie, Borg Jean-Paul, Chang Chenbei, Wang Jianbo
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University Blvd, Birmingham, AL, 35294, USA.
Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Equipe labellisée Ligue 'Cell Polarity, Cell Signaling And Cancer', Marseille, France.
Nat Commun. 2025 Mar 11;16(1):2425. doi: 10.1038/s41467-025-57658-0.
Convergent extension (CE) is a universal morphogenetic engine that promotes polarized tissue extension. In vertebrates, CE is regulated by non-canonical Wnt ligands signaling through "core" proteins of the planar cell polarity (PCP) pathway, including the cytoplasmic protein Dishevelled (Dvl), receptor Frizzled (Fz) and tetraspan protein Van gogh-like (Vangl). PCP was discovered in Drosophila to coordinate polarity in the plane of static epithelium, but does not regulate CE in flies. Existing evidence suggests that adopting PCP for CE might be a vertebrate-specific adaptation with incorporation of new regulators. Herein we use Xenopus to investigate Dact1, a chordate-specific protein. Dact1 induces Dvl to form oligomers that dissociate from Vangl, but stay attached with Fz as signalosome-like clusters and co-aggregate with Fz into protein patches upon non-canonical Wnt induction. Functionally, Dact1 antagonizes Vangl, and synergizes with wild-type Dvl but not its oligomerization-defective mutants. We propose that, by promoting Dvl oligomerization, Dact1 couples Dvl binding partner switch with signalosome-like cluster formation to initiate non-canonical Wnt signaling during vertebrate CE.
汇聚延伸（CE）是一种促进极化组织延伸的通用形态发生机制。在脊椎动物中，CE由非经典Wnt配体通过平面细胞极性（PCP）途径的“核心”蛋白进行调控，这些蛋白包括细胞质蛋白Dishevelled（Dvl）、受体卷曲蛋白（Fz）和四跨膜蛋白类梵高蛋白（Vangl）。PCP最初在果蝇中被发现，用于协调静态上皮平面中的极性，但在果蝇中并不调控CE。现有证据表明，将PCP用于CE可能是脊椎动物特有的适应性变化，并纳入了新的调控因子。在此，我们利用非洲爪蟾研究一种脊索动物特异性蛋白Dact1。Dact1诱导Dvl形成寡聚体，这些寡聚体与Vangl解离，但在非经典Wnt诱导下与Fz结合形成信号小体样簇，并与Fz共同聚集形成蛋白斑。在功能上，Dact1拮抗Vangl，并与野生型Dvl协同作用，但不与寡聚化缺陷型突变体协同作用。我们提出，通过促进Dvl寡聚化，Dact1将Dvl结合伙伴的转换与信号小体样簇的形成联系起来，从而在脊椎动物CE过程中启动非经典Wnt信号传导。
