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Abstract:
The first homolog of Kon-tiki (Kon) was identified in human melanoma cells over 30 ago. However, numerous aspects of the function of Kon and its homologues are poorly understood, including how their three protein domain types, the lamininG domains, the chondroitin sulphate proteoglycan (CSPGs) repeats, and the PDZ-binding domain, interplay to mediate a multitude of biological processes. This study shed light on this question, using Drosophila myogenesis as a model system. Here, a kon genomic fosmid clone derived toolkit, which recapitulates the expression profile of endogenous kon, was applied to investigate how Kon adapts its activity in two distinct developmental scenarios: one in the embryo, in which the small larval muscles form, and a second one in the pupae, in which the larger adult muscles form. This study showed that a compact version of Kon, missing the long CSPG domains is sufficient for building the smaller larval muscles. However, during formation of larger muscles, this compact version is not sufficient, requiring thus to be synergized by the CSPG domains. Furthermore, this study identified the extracellular domain type, which renders Kon able to mediate myotube guidance, the CSPG domains. This is the first in vivo study, which establishes a link between guidance and Kon, thus providing insights to how Kon homologues, NG2/CSPG4, may increase the metastatic potential of melanomas or of soft tissue sarcoma.
