Abstract
ABSTRACTDevelopment and tissue homeostasis rely on the tight regulation of morphogen secretion. In the Drosophila wing imaginal disc epithelium, Wg secretion for long-range signal transduction occurs after apical Wg entry into the endosomal system, followed by secretory endosomal transport. Although Wg release appears to occur from the apical and basal cell sides, its exact post-endocytic fate and the functional relevance of polarized endosomal Wg trafficking are poorly understood. Here, we identify the kinesin-3 family member Klp98A as the master regulator of intracellular Wg transport after apical endocytosis. In the absence of Klp98A, functional mature endosomes accumulate in the apical cytosol, and endosome transport to the basal cytosol is perturbed. Despite the resulting Wg mislocalization, Wg signal transduction occurs normally. We conclude that transcytosis-independent routes for Wg trafficking exist and demonstrate that Wg can be recycled apically via Rab4-recycling endosomes in the absence of Klp98A.
Highlights
During development, formation of a Wnt gradient is necessary for the regulation of cell proliferation and differentiation (Nusse and Clevers, 2017)
Wg mislocalizes to the apical cytosol in the absence of kinesin motor Kinesin-like protein 98A (Klp98A) To understand the relevance of kinesin-mediated transport of Wg along the microtubule network for Wg secretion, we conducted an in vivo RNA interference (RNAi) screen in Drosophila wing imaginal discs
The wing imaginal disc is a well-established model system in which to study the Wg secretory pathway. It is an epithelial sac-like structure composed of a polarized epithelium, the disc proper, and an outer squamous cell layer, the peripodial membrane (Fig. 1A)
Summary
Formation of a Wnt gradient is necessary for the regulation of cell proliferation and differentiation (Nusse and Clevers, 2017). A prerequisite for the controlled delivery of Wnt from its source to its target cells is the tight regulation of secretory trafficking and the temporal and spatial control of release into the extracellular space. To fine-tune extracellular Wnt levels and to orchestrate long- and short-range Wnt signaling, different routes for Wnt release exist. How Wnt is guided into these respective secretory pathways and the molecular mechanisms involved in directed Wnt trafficking are not yet understood. Secretory Wnt trafficking can be studied in the polarized Drosophila wing imaginal disc epithelium, where Wingless Wnt1) secretion from the dorsoventral boundary, with concentration-dependent activation of signaling, coordinates wing
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