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 |
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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. |
doi_str_mv | 10.1016/j.cell.2006.04.009 |
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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. 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Pelte, Nadège ; Ingelfinger, Dierk ; Boutros, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-1884caa470ee35a3a14fa4d4b6aa5815415fafd6cb7737c3087b4379b31e52db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Body Patterning - genetics</topic><topic>Cell Line</topic><topic>Cell Lineage - genetics</topic><topic>Cells, Cultured</topic><topic>Clone Cells - metabolism</topic><topic>Conserved Sequence - genetics</topic><topic>Drosophila</topic><topic>Drosophila melanogaster - embryology</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila melanogaster - metabolism</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - isolation & purification</topic><topic>Drosophila Proteins - metabolism</topic><topic>Evolution, Molecular</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - isolation & purification</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - isolation & purification</topic><topic>Membrane Proteins - metabolism</topic><topic>Mutation - genetics</topic><topic>Phenotype</topic><topic>RNA Interference</topic><topic>Signal Transduction - physiology</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bartscherer, Kerstin</creatorcontrib><creatorcontrib>Pelte, Nadège</creatorcontrib><creatorcontrib>Ingelfinger, Dierk</creatorcontrib><creatorcontrib>Boutros, Michael</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bartscherer, Kerstin</au><au>Pelte, Nadège</au><au>Ingelfinger, Dierk</au><au>Boutros, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Secretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2006-05-05</date><risdate>2006</risdate><volume>125</volume><issue>3</issue><spage>523</spage><epage>533</epage><pages>523-533</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>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. 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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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