ArticleThe Journal of clinical investigation2020
Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Roles of ER Membrane Protein Complex in Protein Biogenesis and Quality Control in the Lung and Beyond.Cell proliferation · 2026Review
- A microscopy-based CRISPR screening platform enables organellar functional genomics and illuminates ciliary biology.Developmental cell · 2026Article
- Analysis of familial exudative vitreoretinopathy (FEVR) cases in the UK 100 000 genomes project increases diagnostic rate and implicates heterozygousJournal of medical genetics · 2026Article
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- METTL3-dependent mCell death & disease · 2024Article
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- The endoplasmic reticulum membrane protein complex subunitGenes & diseases · 2024Article
- Technologies to Study Genetics and Molecular Pathways.Advances in experimental medicine and biology · 2024Review
- Defective EMC1 drives abnormal retinal angiogenesis via Wnt/β-catenin signaling and may be associated with the pathogenesis of familial exudative vitreoretinopathy.Genes & diseases · 2023Article
- Expanding EMC foldopathies: Topogenesis deficits alter the neural crest.Genesis (New York, N.Y. : 2000) · 2023Article
- Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells.Nature communications · 2023Article
- Novel compound heterozygous variants inFrontiers in molecular neuroscience · 2023Article
- De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in Drosophila.Human molecular genetics · 2022Article
- The ER membrane protein complex subunit Emc3 controls angiogenesis via the FZD4/WNT signaling axis.Science China. Life sciences · 2021Article
- Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients.eLife · 2020Article
- Squaring the EMC - how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis.Journal of cell science · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Multipass membrane proteins have a myriad of functions, including transduction of cell-cell signals, ion transport, and photoreception. Insertion of these proteins into the membrane depends on the endoplasmic reticulum (ER) membrane protein complex (EMC). Recently, birth defects have been observed in patients with variants in the gene encoding a member of this complex, EMC1. Patient phenotypes include congenital heart disease, craniofacial malformations, and neurodevelopmental disease. However, a molecular connection between EMC1 and these birth defects is lacking. Using Xenopus, we identified defects in neural crest cells (NCCs) upon emc1 depletion. We then used unbiased proteomics and discovered a critical role for emc1 in WNT signaling. Consistent with this, readouts of WNT signaling and Frizzled (Fzd) levels were reduced in emc1-depleted embryos, while NCC defects could be rescued with β-catenin. Interestingly, other transmembrane proteins were mislocalized upon emc1 depletion, providing insight into additional patient phenotypes. To translate our findings back to humans, we found that EMC1 was necessary for human NCC development in vitro. Finally, we tested patient variants in our Xenopus model and found the majority to be loss-of-function alleles. Our findings define molecular mechanisms whereby EMC1 dysfunction causes disease phenotypes through dysfunctional multipass membrane protein topogenesis.
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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.