Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein

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 fa...

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Veröffentlicht in:Cell 2006-05, Vol.125 (3), p.523-533
Hauptverfasser: Bartscherer, Kerstin, Pelte, Nadège, Ingelfinger, Dierk, Boutros, Michael
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container_end_page 533
container_issue 3
container_start_page 523
container_title Cell
container_volume 125
creator Bartscherer, Kerstin
Pelte, Nadège
Ingelfinger, Dierk
Boutros, Michael
description 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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subjects Animals
Body Patterning - genetics
Cell Line
Cell Lineage - genetics
Cells, Cultured
Clone Cells - metabolism
Conserved Sequence - genetics
Drosophila
Drosophila melanogaster - embryology
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - isolation & purification
Drosophila Proteins - 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
title Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein
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