ArticleDevelopmental cell2020
A Membrane-Tethered Ubiquitination Pathway Regulates Hedgehog Signaling and Heart Development.
Article in Developmental cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Receptor allostery promotes context-specific Sonic Hedgehog signaling during embryonic development.Nature communications · 2026Article
- K63-linked ubiquitin chains mark inactive Smoothened for packaging into ciliary extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- MEGF8 controls osteogenic differentiation through post-transcriptional regulation of BMP-SMAD signaling in craniosynostosis.Cell death and differentiation · 2026Article
- Design principles of a membrane-spanning ubiquitin ligase.Molecular cell · 2026Article
- MGRN1 in development and disease: a unifying view of a versatile membrane-tethered E3 ubiquitin ligase.Biochemical Society transactions · 2026Review
- Article
- [Molecular cancer · 2026Article
- Structural and functional brain asymmetry in relation to heterogeneous causes of situs inversus totalis.Brain structure & function · 2026Article
- Experience-dependent reconfiguration of thermoreceptors regulates neuronal response plasticity.Current biology : CB · 2026Article
- Glial cells in the heart: Implications for their roles in health and disease.The Journal of physiology · 2026Review
- Broadening horizons: new links between cilia and heart development and disease.Frontiers in cardiovascular medicine · 2026Review
- The E3 ubiquitin ligase MGRN1 targets melanocortin receptors MC1R and MC4R via interactions with transmembrane adapters.Journal of cell science · 2025Article
- Maternal cholesterol deficiency predisposes congenital heart defects risk.Signal transduction and targeted therapy · 2025Article
- Loss-of-function variants in ciliary genes confer high risk for tetralogy of Fallot.Science advances · 2025Article
- "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025Article
- Combination of rapamycin and adipose-derived mesenchymal stromal cells enhances therapeutic potential for osteoarthritis.Stem cell research & therapy · 2025Article
- Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.bioRxiv : the preprint server for biology · 2025Article
- The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients.European journal of human genetics : EJHG · 2024Article
- Molecular Pathways and Animal Models of Defects in Situs.Advances in experimental medicine and biology · 2024Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
The etiology of congenital heart defects (CHDs), which are among the most common human birth defects, is poorly understood because of its complex genetic architecture. Here, we show that two genes implicated in CHDs, Megf8 and Mgrn1, interact genetically and biochemically to regulate the strength of Hedgehog signaling in target cells. MEGF8, a transmembrane protein, and MGRN1, a RING superfamily E3 ligase, assemble to form a receptor-like ubiquitin ligase complex that catalyzes the ubiquitination and degradation of the Hedgehog pathway transducer Smoothened. Homozygous Megf8 and Mgrn1 mutations increased Smoothened abundance and elevated sensitivity to Hedgehog ligands. While mice heterozygous for loss-of-function Megf8 or Mgrn1 mutations were normal, double heterozygous embryos exhibited an incompletely penetrant syndrome of CHDs with heterotaxy. Thus, genetic interactions can arise from biochemical mechanisms that calibrate morphogen signaling strength, a conclusion broadly relevant for the many human diseases in which oligogenic inheritance is emerging as a mechanism for heritability.
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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.