ArticleProceedings of the National Academy of Sciences of the United States of America2018
TMEM59 potentiates Wnt signaling by promoting signalosome formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Single-Cell Analysis Combined with Mendelian Randomization Identifies Genes Associated with Prostate Cancer Cells.The world journal of men's health · 2026Article
- Wnt signalosomes: What we know that we do not know.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.Life science alliance · 2024Article
- Article
- Screening and Identification of ssDNA Aptamers for Low-Density Lipoprotein (LDL) Receptor-Related Protein 6.Molecules (Basel, Switzerland) · 2023Article
- Aberrant Cholesterol Metabolism and Wnt/β-Catenin Signaling Coalesce via Frizzled5 in Supporting Cancer Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.Cell discovery · 2022Article
- Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities.Signal transduction and targeted therapy · 2022Review
- A transmembrane protein family gene signature for overall survival prediction in osteosarcoma.Frontiers in genetics · 2022Article
- Dcf1 induces glioblastoma cells apoptosis by blocking autophagy.Cancer medicine · 2022Article
- Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis.Nature communications · 2021Article
- WNT as a Driver and Dependency in Cancer.Cancer discovery · 2021Review
- Whole exome sequencing, in silico and functional studies confirm the association of theSaudi journal of biological sciences · 2021Article
- Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome.Development, growth & differentiation · 2021Review
- Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis.International journal of hematology · 2021Article
- LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence.Frontiers in cell and developmental biology · 2021Review
- Wnt-inducible Lrp6-APEX2 interacting proteins identify ESCRT machinery and Trk-fused gene as components of the Wnt signaling pathway.Scientific reports · 2020Article
- TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities.Cell death & disease · 2020Article
- eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled.The Journal of biological chemistry · 2020Article
- Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion.Cellular and molecular life sciences : CMLS · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt/β-catenin signaling controls development and adult tissue homeostasis by regulating cell proliferation and cell fate decisions. Wnt binding to its receptors Frizzled (FZD) and low-density lipoprotein-related 6 (LRP6) at the cell surface initiates a signaling cascade that leads to the transcription of Wnt target genes. Upon Wnt binding, the receptors assemble into large complexes called signalosomes that provide a platform for interactions with downstream effector proteins. The molecular basis of signalosome formation and regulation remains elusive, largely due to the lack of tools to analyze its endogenous components. Here, we use internally tagged Wnt3a proteins to isolate and characterize activated, endogenous Wnt receptor complexes by mass spectrometry-based proteomics. We identify the single-span membrane protein TMEM59 as an interactor of FZD and LRP6 and a positive regulator of Wnt signaling. Mechanistically, TMEM59 promotes the formation of multimeric Wnt-FZD assemblies via intramembrane interactions. Subsequently, these Wnt-FZD-TMEM59 clusters merge with LRP6 to form mature Wnt signalosomes. We conclude that the assembly of multiprotein Wnt signalosomes proceeds along well-ordered steps that involve regulated intramembrane interactions.
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Registered trials
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.