Signal transduction: Wnt signalling shows its versatility

The Wnt protein Wingless (Wg) functions as a signal in patterning of both the Drosophila embryo and imaginal discs. Lack of porcupine (porc) activity is associated with mutant phenotypes similar to those of wg mutations. In porc mutant embryos, Wg protein is confined to the cells that produce it, suggesting that Porc plays a role in processing or secretion of Wg. porc encodes a novel transmembrane protein that appears to be concentrated at the endoplasmic reticulum. We present both genetic and in vitro evidence demonstrating that porc is involved specifically in the processing of Wg. We identified a human sequence related to Porc suggesting the existence of a family of proteins involved in processing of Wnts.

During C. elegans development, Wnt/WG signaling is required for differences in cell fate between sister cells born from anterior/posterior divisions. A beta-catenin-related gene, wrm-1, and the lit-1 gene are effectors of this signaling pathway and appear to downregulate the activity of POP-1, a TCF/LEF-related protein, in posterior daughter cells. We show here that lit-1 encodes a serine/threonine protein kinase homolog related to the Drosophila tissue polarity protein Nemo. We demonstrate that the WRM-1 protein binds to LIT-1 in vivo and that WRM-1 can activate the LIT-1 protein kinase when coexpressed in vertebrate tissue culture cells. This activation leads to phosphorylation of POP-1 and to apparent changes in its subcellular localization. Our findings provide evidence for novel regulatory avenues for an evolutionarily conserved Wnt/WG signaling pathway.

In a four-cell-stage Caenorhabditis elegans embryo, Wnt signaling polarizes an endoderm precursor called EMS. The polarization of this cell orients its mitotic spindle in addition to inducing endodermal fate in one daughter cell. Reducing the function of Wnt pathway genes, including a newly identified GSK-3beta homolog called gsk-3, disrupts endoderm induction, whereas only a subset of these genes is required for proper EMS mitotic spindle orientation. Wnt pathway genes thought to act downstream of gsk-3 appear not to be required for spindle orientation, suggesting that gsk-3 represents a branch point in the control of endoderm induction and spindle orientation. Orientation of the mitotic spindle does not require gene transcription in EMS, suggesting that Wnt signaling may directly target the cytoskeleton in a responding cell.