Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle. From initial, symmetric subcellular distributions in pupal wing cells, Frizzled and Dishevelled become highly enriched at the distal portion of the cell cortex. We describe a Prickle-dependent intercellular feedback loop that generates asymmetric Frizzled and Dishevelled localization. In the absence of Prickle, Frizzled and Dishevelled remain symmetrically distributed. Prickle localizes to the proximal side of pupal wing cells and binds the Dishevelled DEP domain, inhibiting Dishevelled membrane localization and antagonizing Frizzled accumulation. This activity is linked to Frizzled activity on the adjacent cell surface. Prickle therefore functions in a feedback loop that amplifies differences between Frizzled levels on adjacent cell surfaces.
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http://dx.doi.org/10.1016/s0092-8674(02)00715-8 | DOI Listing |
In Silico Pharmacol
November 2024
Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M.Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapur, Karnataka 586103 India.
Modulation of the Wnt/β-catenin signaling pathway may aid in discovering new medications for the effective management of pulmonary artery hypertension (PAH). Given the therapeutic potential of Mucuna pruriens in several diseases, the present study aimed to analyze interactions of different bioactive compounds of Mucuna pruriens plant seeds with Wnt/β-catenin pathway targeting its various components like Wnt 3a, Frizzled 1, LRP 5/6, β-catenin, Disheveled, cyclin D1 by in silico analysis. The proposed work is based on computational analysis including ADME/T properties, by a Swiss ADME server.
View Article and Find Full Text PDFGenes Dis
January 2025
NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin 300134, China.
Naked cuticle homolog 2 (NKD2) has been recognized as an antagonist of Wnt/β-catenin signaling and a tumor suppressor. The role of NKD2 in osteoblast and osteoclast differentiation and the mechanism are not fully understood. In this study, we identified the up-regulation of NKD2 during osteoblast and adipocyte differentiation.
View Article and Find Full Text PDFCurr Cardiol Rev
October 2024
Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
The increasing incidences of morbidity and mortality associated with cardiovascular diseases represent significant difficulties for clinical treatment and have a major impact on patient health. Wnt signaling pathways are highly conserved and are well known for their regulatory roles in embryonic development, tissue regeneration, and adult tissue homeostasis. Wnt signaling is classified into two distinct pathways: canonical Wnt/β-catenin signaling and noncanonical pathways, including planar cell polarity and Wnt/Ca2+ pathways.
View Article and Find Full Text PDFNat Commun
September 2024
Laboratory of Receptor Structure and Signaling, HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
ACS Sens
September 2024
Department of Physiology & Pharmacology, Section of Receptor Biology & Signaling, Biomedicum, Karolinska Institutet, S-17165 Stockholm, Sweden.
Wingless/Int-1 (WNT) signaling is mediated by WNT binding to 10 Frizzleds (FZD), which propagate the signal inside the cell by interacting with different transducers, most prominently the phosphoprotein Dishevelled (DVL). Despite recent progress, questions about WNT/FZD selectivity and paralog-dependent differences in the FZD/DVL interaction remain unanswered. Here, we present a class-wide analysis of the FZD/DVL interaction using the DEP domain of DVL as a proxy in bioluminescence resonance energy transfer (BRET) techniques.
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