Next Article in Journal
Blueberry Supplementation in Neuronal Health and Protective Technologies for Efficient Delivery of Blueberry Anthocyanins
Next Article in Special Issue
Pharmacological Manipulation of Early Zebrafish Skeletal Development Shows an Important Role for Smad9 in Control of Skeletal Progenitor Populations
Previous Article in Journal
Topical Collection “Pharmacology of Medicinal Plants”
Previous Article in Special Issue
Zebrafish Models of Photoreceptor Dysfunction and Degeneration
Article

Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis

1
Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340 Izmir, Turkey
2
Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340 Izmir, Turkey
3
Institute of Physiology, Switzerland and National Center of Competence in Research NCCR Kidney, University of Zurich, CH-8057 Zurich, Switzerland
4
Institute of Zoology-Developmental Biology, University of Cologne, 50674 Cologne, Germany
5
Science for Life Laboratory, Department of Women’s and Children’s Health, Karolinska Institutet, 17177 Stockholm, Sweden
6
MRC Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, Oxford OX39DS, UK
*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(1), 100; https://doi.org/10.3390/biom11010100
Received: 10 December 2020 / Revised: 5 January 2021 / Accepted: 11 January 2021 / Published: 14 January 2021
(This article belongs to the Special Issue Zebrafish: A Model for the Study of Human Diseases)
Wnt/β-catenin signaling controls many biological processes for the generation and sustainability of proper tissue size, organization and function during development and homeostasis. Consequently, mutations in the Wnt pathway components and modulators cause diseases, including genetic disorders and cancers. Targeted treatment of pathway-associated diseases entails detailed understanding of the regulatory mechanisms that fine-tune Wnt signaling. Here, we identify the neurotrophin receptor-associated death domain (Nradd), a homolog of p75 neurotrophin receptor (p75NTR), as a negative regulator of Wnt/β-catenin signaling in zebrafish embryos and in mammalian cells. Nradd significantly suppresses Wnt8-mediated patterning of the mesoderm and neuroectoderm during zebrafish gastrulation. Nradd is localized at the plasma membrane, physically interacts with the Wnt receptor complex and enhances apoptosis in cooperation with Wnt/β-catenin signaling. Our functional analyses indicate that the N-glycosylated N-terminus and the death domain-containing C-terminus regions are necessary for both the inhibition of Wnt signaling and apoptosis. Finally, Nradd can induce apoptosis in mammalian cells. Thus, Nradd regulates cell death as a modifier of Wnt/β-catenin signaling during development. View Full-Text
Keywords: Nradd; p75 neurotrophin receptor; Wnt/β-catenin signaling; apoptosis; death receptor Nradd; p75 neurotrophin receptor; Wnt/β-catenin signaling; apoptosis; death receptor
Show Figures

Graphical abstract

MDPI and ACS Style

Ozalp, O.; Cark, O.; Azbazdar, Y.; Haykir, B.; Cucun, G.; Kucukaylak, I.; Alkan-Yesilyurt, G.; Sezgin, E.; Ozhan, G. Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis. Biomolecules 2021, 11, 100. https://doi.org/10.3390/biom11010100

AMA Style

Ozalp O, Cark O, Azbazdar Y, Haykir B, Cucun G, Kucukaylak I, Alkan-Yesilyurt G, Sezgin E, Ozhan G. Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis. Biomolecules. 2021; 11(1):100. https://doi.org/10.3390/biom11010100

Chicago/Turabian Style

Ozalp, Ozgun, Ozge Cark, Yagmur Azbazdar, Betul Haykir, Gokhan Cucun, Ismail Kucukaylak, Gozde Alkan-Yesilyurt, Erdinc Sezgin, and Gunes Ozhan. 2021. "Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis" Biomolecules 11, no. 1: 100. https://doi.org/10.3390/biom11010100

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop