Sol narae (Sona) is required for cleavage of exosomal Wingless and generation of a functional Wingless fragment

Abstract

Wnt/Wg family proteins are secreted morphogens essential for embryonic development and adult homeostasis in all metazoans. Mechanisms for the secretion of Wg and composition of extracellular Wg are, however, still largely unknown. Here, I show that a fly ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) named Sol narae (Sona) is essential for larval tissue growth and adult appendage formation. EMS mutagenesis screening was carried out to obtain suppressors that can suppress lethality induced by overexpression of Sona, and one of the suppressors turned out to have a nonsense mutation in wntless (wls) gene. Wls is essential for Wg secretion, suggesting that Sona may be involved in Wg signaling pathway.

Genetic analysis demonstrated that the loss of Sona reduced both Wg signaling and Wg secretion. Sona and Wg specifically colocalized in early endosomes and were enriched on exosomes. Interestingly, Wg fragments were generated on exosomes only in the presence of protease-active Sona, demonstrating that Sona’s protease activity is essential for cleaving Wg. The cleavage separates the soluble C-terminal domain (CTD) from the membrane-bound N-terminal domain (NTD) of Wg. The CTD was uniquely abundant in the region distant from Wg-producing cells. Wg-CTD participates in regulation of cell proliferation, which is one of known Wg activities. Therefore, I propose that Sona is required for the formation of functional CTD that can travel farther than other forms of Wg in extracellular space.