Secretion of Wnt ligands requires Evi, a conserved transmembrane protein

Kerstin Bartscherer; Nadège Pelte; Dierk Ingelfinger; Michael Boutros

doi:10.1016/j.cell.2006.04.009

Secretion of Wnt ligands requires Evi, a conserved transmembrane protein

Cell. 2006 May 5;125(3):523-33. doi: 10.1016/j.cell.2006.04.009.

Authors

Kerstin Bartscherer¹, Nadège Pelte, Dierk Ingelfinger, Michael Boutros

Affiliation

¹ German Cancer Research Center, Boveri-Group Signaling and Functional Genomics, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.

PMID: 16678096
DOI: 10.1016/j.cell.2006.04.009

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. 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*

Substances

Drosophila Proteins
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Wls protein, Drosophila
Wnt Proteins