In vivo evidence for a regulatory role of the kinase activity of the linotte/derailed receptor tyrosine kinase, a Drosophila Ryk ortholog

Abstract

The RYK subfamily of receptor tyrosine kinases is characterised by unusual, but highly conserved, amino acid substitutions in the kinase domain. The linotte/derailed gene encodes a Drosophila RYK subfamily member involved in embryonic and adult central nervous system development. Previous studies have shown that the kinase activity of this receptor is not required in vivo for its embryonic function. In this study, we have investigated the role of the cytoplasmic domain and the kinase activity of the linotte/derailed receptor tyrosine kinase in adult brain development. Our results indicate that these domains are not essential for adult brain development but they are required for the proper regulation of the activity of this receptor. This sheds light on a regulatory role for the kinase activity of a RYK subfamily member.

Respective roles of the DRL receptor and its ligand WNT5 inDrosophilamushroom body development

“…The Wnt5 MB mutant phenotype is most consistent with WNT5 being required for neurite outgrowth. It is striking that these mutant phenotypes resemble those described for lio + /drl + overexpression (Taillebourg et al, 2005) (this study). We propose that this GOF phenotype is due to lio + /drl + expression within or close to MB cells, where the ectopic DRL protein can bind to the WNT5 protein and prevent its function.…”

“…We looked, in the two different genetic combinations with the anti-FASII labeling, to the MB phenotype: UAS-drl: 58 MB (all lobes missing: 0/58; some lobes missing: 2/58; no lobes missing or wild-type-looking: 56/58), UAS-drl⌬intra: 62 MB (all lobes missing: 27/62; some lobes missing: 23/62; no lobes missing or wild-type-looking: 12/62). As was already seen (Taillebourg et al, 2005), the GOF effect is much more effective when the RTK is deleted of its intracellular domain. Therefore, clear MB axon pathfinding defects are obtained when drl⌬intra is overexpressed mainly in the MB cells.…”

“…We show here that Wnt5 mutants have MB defects that can be rescued by expressing Wnt5 cDNA specifically in MB cells. Strikingly, LOF Wnt5 MB phenotypes resemble those induced by drl gain of function (Taillebourg et al, 2005) (this study), and we show that Wnt5 and drl interact genetically. We propose that the gene pair drl and Wnt5 work to build adult MBs, with Wnt5 being required within MB neurons and drl being required within non-MB neurons.…”

“…2B,C and Fig. 3C of Taillebourg et al (Taillebourg et al, 2005)] suggesting an antagonistic interaction between Wnt5 and drl. To confirm that this drl gain-of-function (GOF) phenotype is still present when the expression is mainly restricted to the MB, we overexpressed two In the x-axis label, both the GAL4 line used and the absence (-) or presence (+) of the UAS-drl construct are specified.…”

Src family kinases are required for WNT5 signaling through the Derailed/RYK receptor in theDrosophilaembryonic central nervous system

“…Although DRL function in the Drosophila embryonic CNS does not apparently involve intrinsic tyrosine kinase activity (Yoshikawa et al, 2001), the cytoplasmic domain of DRL is required for axon repulsion (Yoshikawa et al, 2003) and plays a regulatory role in DRL function during brain development (Taillebourg et al, 2005). In addition, mammalian RYK lacking its cytoplasmic domain acts as a dominant-negative protein (Schmitt et al, 2005).…”