The transmembrane receptors Otk and Otk2 function redundantly in Drosophila Wnt signal transduction
von Karen Linnemannstöns
Datum der mündl. Prüfung:2013-01-23
Betreuer:Prof. Dr. Andreas Wodarz
Gutachter:Prof. Dr. Andreas Wodarz
Gutachter:Prof. Dr. Annette Borchers
EnglischCanonical and non-canonical Wnt signaling pathways have in common Frizzled (Fz) as the core Wnt receptor element. Recent findings implicate that not only the choice of Wnt ligands, but also the presence of additional components in the receptor complex determine signaling pathway specificity. Vertebrate PTK7 (protein tyrosine kinase 7) encodes a catalytically inactive receptor-tyrosine kinase and is required for the control of planar cell polarity (PCP) in frogs and mice by acting as Fz co-receptor and inhibiting canonical Wnt signaling. Mutation of a Drosophila homolog of PTK7, the gene off-track (otk), was reported not to cause PCP phenotypes in the fly, but is suggested to block canonical Wingless signaling in embryonic patterning. We found that in contrast to previous reports, flies homozygous for a complete knock-out of otk are viable and fertile and indeed do not show PCP phenotypes. However, we discovered an otk paralog (otk2, CG8964). Otk and Otk2 are co-expressed throughout embryonic and larval development. They are highly expressed in the visceral mesoderm as well as in the nervous system and enriched at anterior commissures. Otk and Otk2 interact biochemically and possibly function redundantly in Wnt signal transduction. Surprisingly, flies homozygous for a double knock-out of otk and otk2 are viable as well and neither show PCP nor Wingless signaling phenotypes. However, otk,otk2 double mutants are male sterile due to an obstruction in the ejaculatory duct and this is possibly linked to disturbed Wnt2 signaling. Overall defects in the nervous system cannot be observed, most likely because only a subset of neurons is affected. This could be explained by the abundance of receptors and co-receptors acting in a redundant manner. Indeed, expression data suggest a possible connection to Wnt5/Drl signaling. Furthermore, genetic and biochemical studies revealed that Otk/Otk2 genetically and biochemically interact with fz1, indicating that Otk/Otk2 might also function as Fz1 co-receptors in the signal transduction of Wingless or other members of the Wnt family under certain circumstances. These results suggests that Otk and Otk2 function as redundant receptors in several Drosophila Wnt signaling pathways, including Wnt2 as well as Wnt5/Drl signaling.
Keywords: Wingless; Off-track; PTK7; Wnt