Article
Multidisciplinary Sciences
Gonzalo J. Beitia, Trevor J. Rutherford, Stefan M. Freund, Hugh R. Pelham, Mariann Bienz, Melissa Gammons
Summary: The study reveals that intermolecular contacts in the DEP dimer of Dishevelled protein play a crucial role in its stability and function in relaying canonical Wnt signals, and these contacts are mediated by a phosphorylation site that can regulate the protein's activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Mingyi Li, Jing Zheng, Dong Luo, Kai Xu, Ren Sheng, Bryan T. MacDonald, Xi He, Xinjun Zhang
Summary: The membrane-tethered protease Tiki inhibits Wnt signaling by cleaving and inactivating Wnt3a. It requires Frizzled (FZD) receptors to antagonize Wnt signaling at the cell surface. Tiki cleaves the N-terminus of Wnt3a or Wnt5a in the Wnt-FZD complex, preventing the recruitment and activation of coreceptors.
Article
Multidisciplinary Sciences
Anja Bufe, Ana Garcia del Arco, Magdalena Hennecke, Anchel de Jaime-Soguero, Matthias Ostermaier, Yu-Chih Lin, Anja Ciprianidis, Janina Hattemer, Ulrike Engel, Petra Beli, Holger Bastians, Sergio P. Acebron
Summary: Canonical Wnt signaling is crucial for development and tissue renewal by regulating beta-catenin target genes, while non-canonical Wnt signaling is also involved in mitosis. This study identified the role of Wnt signaling in regulating KIF2A during cell division, which is essential for chromosome alignment. Dishevelled recruits KIF2A and Wnt signaling modulates KIF2A interaction with PLK1, highlighting the importance of Wnt signaling in cell division and genome maintenance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Victoria H. Ng, Zachary Spencer, Leif R. Neitzel, Anmada Nayak, Matthew A. Loberg, Chen Shen, Sara N. Kassel, Heather K. Kroh, Zhenyi An, Christin C. Anthony, Jamal M. Bryant, Amanda Lawson, Lily Goldsmith, Hassina Benchabane, Amanda G. Hansen, Jingjing Li, Starina D'Souza, Andres M. Lebensohn, Rajat Rohatgi, William A. Weiss, Vivian L. Weiss, Charles Williams, Charles C. Hong, David J. Robbins, Yashi Ahmed, Ethan Lee
Summary: The study identifies the USP46 deubiquitylase complex as a positive regulator of Wnt signaling in various organisms. The complex inhibits the degradation of cell surface LRP6, thereby enhancing Wnt signaling. The authors propose a model for the assembly of the complex and its role in Wnt signaling.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Jian Chen, Jia Liu, Shimin Chen, Ruijun Lai, Chuanchuan Zheng, Jialiang Lu, Xinshao Jiang, Feng He, Chengliang Yang, Kai Li, Kegong Xie, Yujin Tang, Liqiang Wang
Summary: Salinomycin may be a promising therapeutic drug for osteoarthritis (OA) as it has shown protective effects on cartilage cells, reduces disease-associated changes, and delays cartilage destruction and osteophyte formation. Its mechanism of action may involve regulating cell synthesis and inhibiting degradation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ellen Youngsoo Rim, Hans Clevers, Roel Nusse
Summary: The Wnt pathway plays a central role in developmental and disease-related processes, regulating the generation and spatial arrangement of different cell types. Through regulation of cell fate, mitotic activity, and cell polarity, Wnt signaling coordinates development and tissue homeostasis, and its dysregulation is implicated in various disorders. This review summarizes the advances in our understanding of this pathway, from Wnt protein production to signal transduction in receiving cells. The evolutionary history of this pathway, as well as its regulators, and the remaining gaps in knowledge are discussed, highlighting directions for future research.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Lizbeth Garcia-Velazquez, Paulina Lopez-Carrasco, Clorinda Arias
Summary: This study analyzed the expression levels and protein content of different molecules of the Wnt pathway in different brain regions, and discussed their correlation with changes in synaptic number and morphology. It was found that the downregulation of the Wnt pathway in the aged brain is not associated with changes in the number and structure of central synapses.
EXPERIMENTAL GERONTOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Erin A. Nekritz, Ruth Rodriguez-Barrueco, Koon-Kiu Yan, Meredith L. Davis, Rachel L. Werner, Laura Devis-Jauregui, Partha Mukhopadhyay, Jiyang Yu, David Llobet-Navas, Jose Silva
Summary: The miR-424/503 cluster plays a crucial role in regulating Wnt signaling, MaSC fate, and breast cancer development, with its function involving targeting the LRP6 co-receptor to reduce its expression.
Article
Biochemistry & Molecular Biology
Harminder D. Singh, Jian-xing Ma, Yusuke Takahashi
Summary: By individually knocking out LRP5 and LRP6 in a human retinal pigment epithelium cell line, it was discovered that Wnt ligands can activate Wnt signaling through different co-receptors, indicating differential roles of LRP5 and LRP6 in Wnt signaling regulation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cell Biology
Qian Ren, Jiongcheng Chen, Youhua Liu
Summary: LRP5 and LRP6 are crucial in mediating Wnt signaling, with similar functions but also distinct characteristics, as they interact with different protein partners, each possessing its own unique functions. Understanding the precise roles of LRP5 and LRP6 may help in identifying and refining therapeutic targets for various human diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Environmental Sciences
Saifang Fu, Rongbang Tan, Yufei Feng, Ping Yu, Yuqian Mo, Wei Xiao, Shouyu Wang, Jingjing Zhang
Summary: This study revealed that N-methyl-N-nitrosourea (MNU) induced aberrant angiogenesis through the modulation of the rspo1/Wnt/β-catenin/vegfaa axis. Furthermore, it was found that the pro-angiogenic effect of MNU on developing zebrafish embryos could be controlled through pharmacological manipulation.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Review
Cell Biology
Wonyoung Jeong, Eek-hoon Jho
Summary: Wnt signaling pathway, particularly Wnt/beta-catenin signaling, is crucial in development and tissue homeostasis, with dysregulation of components like LRP6 implicated in diseases such as cancer, neurodegeneration, metabolic syndrome, and skeletal disease. The molecular mechanisms by which LRP6 senses Wnt and transduces downstream signaling cascades are still being deciphered, highlighting the complexity and importance of this pathway in various physiological and pathological processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jacob P. Mahoney, Elise S. Bruguera, Mansi Vasishtha, Lauren B. Killingsworth, Saw Kyaw, William Weis
Summary: In the Wnt-beta-catenin pathway, Fzd-Dvl binding is enhanced by increased concentration of PI(4,5)P-2, generated by Dvl-associated lipid kinases in response to Wnt. However, binding to Fzd does not promote Dvl DEP domain dimerization.
Article
Genetics & Heredity
Huadong Yin, Shunshun Han, Can Cui, Yan Wang, Diyan Li, Qing Zhu
Summary: The study demonstrates that plec plays a crucial role in skeletal muscle development by promoting myoblast differentiation and proliferation, inhibiting apoptosis, regulating atrophy-related genes, and forming a protein complex with Dishevelled-2 to activate Wnt signaling. Additionally, plec resists ubiquitination, reduces autophagy, and stabilizes Dvl-2 to modulate canonical Wnt signaling and skeletal development.
Article
Biochemistry & Molecular Biology
S. Zachary Swartz, Tzer Han Tan, Margherita Perillo, Nikta Fakhri, Gary M. Wessel, Athula H. Wikramanayake, Iain M. Cheeseman
Summary: In meiotic oocytes of the sea star Patifia miniata, the distribution dynamics of the Disheveled protein are regulated by meiotic cell cycle progression and influenced by association with Lamp1+ endosomes and pre-localized Frizzled receptors within the oocyte cortex.