ArticleScientific reports2016
The γ-Protocadherin-C3 isoform inhibits canonical Wnt signalling by binding to and stabilizing Axin1 at the membrane.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- DNA methylation profiling identifies long-range epigenetic silencing of clustered protocadherins as a key determinant of meningioma progression.Nature communications · 2026Article
- Article
- PCDHGC3 silencing promotes clear cell renal cell carcinoma metastasis via mTOR/HIF2α activation, lipid metabolism rewiring, and ferroptosis evasion.Cell death & disease · 2026Article
- Reduced Neuronal Self-Avoidance in Mouse Starburst Amacrine Cells With Only One Pcdhg Isoform.Developmental neurobiology · 2026Article
- Article
- Protocadherin γC4 Promotes Neuronal Survival in the Mouse Retina Through Its Variable Cytoplasmic Domain.Molecular neurobiology · 2025Article
- ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.Molecular psychiatry · 2025Article
- Reduced neuronal self-avoidance in mouse starburst amacrine cells with only onebioRxiv : the preprint server for biology · 2025Article
- Structural insights into the in situ assembly of clustered protocadherin γB4.Nature communications · 2025Article
- Clustered protocadherinProceedings of the National Academy of Sciences of the United States of America · 2024Article
- A C-terminal motif containing a PKC phosphorylation site regulates γ-Protocadherin-mediated dendrite arborization in the cerebral cortex in vivo.Developmental neurobiology · 2024Article
- [Exploring the Role of PCDHGB4 in the Occurrence of Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- The scaffold protein AXIN1: gene ontology, signal network, and physiological function.Cell communication and signaling : CCS · 2024Review
- The Role of Protocadherin γ in Adult Sensory Neurons and Skin Reinnervation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons.Neuron · 2023Article
- A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients.Journal of pain research · 2023Article
- Ubiquitination of the protocadherin-γA3 variable cytoplasmic domain modulates cell-cell interaction.Frontiers in cell and developmental biology · 2023Article
- Protocadherin gamma C3: a new player in regulating vascular barrier function.Neural regeneration research · 2023Review
- Protocadherin Gamma C3 (PCDHGC3) Is Strongly Expressed in Glioblastoma and Its High Expression Is Associated with Longer Progression-Free Survival of Patients.International journal of molecular sciences · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The 22 γ-Protocadherin (γ-Pcdh) adhesion molecules encoded by the Pcdhg gene cluster play critical roles in nervous system development, including regulation of dendrite arborisation, neuronal survival, and synaptogenesis. Recently, they have been implicated in suppression of tumour cell growth by inhibition of canonical Wnt signalling, though the mechanisms through which this occurs remain unknown. Here, we show differential regulation of Wnt signalling by individual γ-Pcdhs: The C3 isoform uniquely inhibits the pathway, whilst 13 other isoforms upregulate signalling. Focusing on the C3 isoform, we show that its unique variable cytoplasmic domain (VCD) is the critical one for Wnt pathway inhibition. γ-Pcdh-C3, but not other isoforms, physically interacts with Axin1, a key component of the canonical Wnt pathway. The C3 VCD competes with Dishevelled for binding to the DIX domain of Axin1, which stabilizes Axin1 at the membrane and leads to reduced phosphorylation of Wnt co-receptor Lrp6. Finally, we present evidence that Wnt pathway activity can be modulated up (by γ-Pcdh-A1) or down (by γ-Pcdh-C3) in the cerebral cortex in vivo, using conditional transgenic alleles. Together, these data delineate opposing roles for γ-Pcdh isoforms in regulating Wnt signalling and identify Axin1 as a novel protein interactor of the widely-expressed γ-Pcdh-C3 isoform.
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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.