Evidence map›Paper›PMID 39463927›Full record

ArticlebioRxiv : the preprint server for biology2025

Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL.

Dong Luo, Jing Zheng, Shuning Lv, Ren Sheng, Maorong Chen, Xi He, Xinjun Zhang

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Dong LuoKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Jing ZhengKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Shuning LvKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Ren ShengCollege of Life and Health Science, Northeastern University, Shenyang, China.ORCID 0000-0002-2293-8986
Maorong ChenCenter for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.ORCID 0000-0003-3744-8864
Xi HeThe F. M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8093-7981
Xinjun ZhangKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.ORCID 0000-0003-2409-4104

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Wnt-LRP interaction in Wnt signal transductionR01GM057603 · NIGMS · CHILDREN'S HOSPITAL BOSTON · PI HE, XI · 1999 to 2018
$6.3M
Wnt Signaling and Vertebrate embryogenesisR35GM134953 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI HE, XI · 2020 to 2024
$3.8M
NICHD NIH HHS P50 HD105351NIGMS NIH HHS R01 GM057603NIGMS NIH HHS R35 GM134953
6 · The paper itself

Abstract

Frizzled (FZD) proteins are the principal receptors of the Wnt signaling pathway. However, whether Wnt ligands induce FZD endocytosis and degradation remains elusive. The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 were reported to promote the endocytosis and degradation of FZD receptors to inhibit Wnt signaling, and their function is antagonized by R-spondin (RSPO) proteins. However, the dependency of RSPO-ZNRF3/RNF43-mediated FZD endocytosis and degradation on Wnt stimulation, as well as the specificity of this degradation for different FZD, remains unclear. Here, we demonstrated that Wnt induces FZD5/8 endocytosis and degradation in a ZNRF3/RNF43-dependent manner. ZNRF3/RNF43 selectively targets FZD5/8 for degradation upon Wnt stimulation. RSPO1 enhances Wnt signaling by specifically stabilizing FZD5/8. Wnt promotes the interaction between FZD5 and RNF43. We further demonstrated that DVL proteins promote ligand-independent endocytosis of FZD but are dispensable for Wnt-induced FZD5/8 endocytosis and degradation. Our results reveal a novel negative regulatory mechanism of Wnt signaling at the receptor level and illuminate the mechanism by which RSPO-ZNRF3/RNF43 regulates Wnt signaling, which may provide new insights into regenerative medicine and cancer therapy.

Identifiers

PMID39463927
PMCPMC11507892

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.