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Bartscherer, K, Pelte, N, Ingelfinger, D and Boutros, M (2006) Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125:523-33


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.


PubMed Online version:10.1016/j.cell.2006.04.009


Animals; Body Patterning/genetics; Cell Line; Cell Lineage/genetics; Cells, Cultured; Clone Cells/metabolism; Conserved Sequence/genetics; Drosophila Proteins/genetics; Drosophila Proteins/isolation & purification; Drosophila Proteins/metabolism; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Evolution, Molecular; Gene Expression Regulation, Developmental/physiology; Humans; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/isolation & purification; Intracellular Signaling Peptides and Proteins/metabolism; Membrane Proteins/genetics; Membrane Proteins/isolation & purification; Membrane Proteins/metabolism; Mutation/genetics; Phenotype; RNA Interference; Signal Transduction/physiology; Wnt Proteins/metabolism; Wnt Proteins/secretion



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

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