Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein
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Wnt signaling pathways are important for multiple biological processes during development and disease. Wnt proteins are secreted factors that activate target-gene expression in both a short- and long-range manner. Currently, little is known about how Wnts are released from cells and which factors facilitate their secretion. Here, we identify a conserved multipass transmembrane protein, Evenness interrupted (Evi/Wls), through an RNAi survey for transmembrane proteins involved in Drosophila Wingless (Wg) signaling. During development, evi mutants have patterning defects that phenocopy wg loss-of-function alleles and fail to express Wg target genes. evi's function is evolutionarily conserved as depletion of its human homolog disrupts Wnt signaling in human cells. Epistasis experiments and clonal analysis place evi in the Wg-producing cell. Our results show that Wg is retained by evi mutant cells and suggest that evi is the founding member of a gene family specifically required for Wg/Wnt secretion.
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The porcupine protein plays an important role in the palmitolation of the Wnt proteins, and their secretion is regulated by the wntless or evenness interrupted proteins and the retromer complex.
“The porcupine protein has been shown to play an important role in the palmitolation of the Wnt proteins, and their secretion is regulated by the wntless or evenness interrupted proteins and the retromer complex.11–14”
From Wnt signal transduction pathways (2008) · cites this paper as [12]
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- Authors
- Bartscherer, K., Pelte, N., Ingelfinger, D., & Boutros, M.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Boutros, Michael
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 125
- Issue
- 3
- Pages
- 523-533
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2067937471
- Cited by
- 580
- References
- 53
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 21 · 2023: 20 · 2022: 24 · 2021: 31 · 2020: 33 · 2019: 34 · 2018: 35 · 2017: 33 · 2016: 35 · 2015: 29 · 2014: 45 · 2013: 29 · 2012: 37
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- Wnt secretion, Wnt signaling, Drosophila, transmembrane proteins, gene family evolution, epistasis, clonal analysis, RNAi screen, developmental patterning
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Clone Cells, Drosophila melanogaster, Humans, Membrane Proteins, Mutation, Phenotype, Signal Transduction, Conserved Sequence, Gene Expression Regulation, Developmental, Cell Lineage, Evolution, Molecular, Body Patterning, Drosophila Proteins, RNA Interference, Intracellular Signaling Peptides and Proteins, Wnt Proteins
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