Abstract
Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass transmembrane protein. Vertebrate protein tyrosine kinase 7 (PTK7) was identified as a Wnt co-receptor required for control of planar cell polarity (PCP) in frogs and mice. We found that flies homozygous for a complete knock-out of the Drosophila PTK7 homolog off track (otk) are viable and fertile and do not show PCP phenotypes. We discovered an otk paralog (otk2, CG8964), which is co-expressed with otk throughout embryonic and larval development. Otk and Otk2 bind to each other and form complexes with Frizzled, Frizzled2 and Wnt2, pointing to a function as Wnt co-receptors. Flies lacking both otk and otk2 are viable but male sterile due to defective morphogenesis of the ejaculatory duct. Overexpression of Otk causes female sterility due to malformation of the oviduct, indicating that Otk and Otk2 are specifically involved in the sexually dimorphic development of the genital tract.
Highlights
Wnt proteins bind at the cell surface to transmembrane receptors, which transduce the signal to downstream components of the various branches of Wnt signal transduction [1]
In addition to members of the Frizzled receptor family, which were the first Wnt receptors to be identified [2], Wnts were shown to bind to the transmembrane proteins low density lipoprotein receptorrelated protein 5/6 (LRP5/6) [3,4], receptor tyrosine kinase-like orphan receptors 1/2 (Ror1/2) [5,6], related to receptor tyrosine kinase (Ryk) [7,8,9], muscle specific kinase (MuSK) [10], syndecan [11] and protein tyrosine kinase 7 (PTK7) [12], reviewed in [13]
planar cell polarity (PCP) phenotypes were observed upon knock-down or mutation of PTK7 in Xenopus [18] and zebrafish [22]
Summary
Wnt proteins bind at the cell surface to transmembrane receptors, which transduce the signal to downstream components of the various branches of Wnt signal transduction [1]. In addition to members of the Frizzled receptor family, which were the first Wnt receptors to be identified [2], Wnts were shown to bind to the transmembrane proteins low density lipoprotein receptorrelated protein 5/6 (LRP5/6) [3,4], receptor tyrosine kinase-like orphan receptors 1/2 (Ror1/2) [5,6], related to receptor tyrosine kinase (Ryk) [7,8,9], muscle specific kinase (MuSK) [10], syndecan [11] and protein tyrosine kinase 7 (PTK7) [12], reviewed in [13]. PTK7 knock-down in Xenopus caused defects in migration of cranial neural crest cells [23], very similar to animals in which the function of Dishevelled, an intracellular component of Wnt signaling, has been impaired [24]
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