The kinesin motor Klp98A mediates apical to basal Wg transport

Abstract

Development 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.

Wnt signalling and endocytosis: Mechanisms, controversies and implications for stress responses

“…A similar role in regulating extracellular Wnt distribution from the source cells had been proposed for retromers in C. elegans , although the exact mechanisms remain unknown (Coudreuse et al., 2006). Interestingly, Wntless and AP2 are dispensable for Wnt transcytosis, substantiating the idea that AP2‐dependent and AP2‐independent endocytosis routes fine‐tune Wnt secretion for forming extracellular Wnt gradients for signalling across various distances (Linnemannstöns et al., 2020; Witte et al., 2020).…”

“…In addition to regulating the recycle and trafficking of Wntless, endocytosis also mediates the intracellular transport of Wnts per se (Linnemannstöns et al., 2020; Witte et al., 2020). In Drosophila imaginal disc tissues, this endocytosis‐dependent Wnt trafficking inside the source cells, also known as transcytosis, has been shown to be critical for distributing extracellular Wnts as long‐range signalling molecules (Pfeiffer and Vincent, 1999; Routledge and Scholpp, 2019; Strigini and Cohen, 2000; Witte et al., 2020).…”

“…In addition to regulating the recycle and trafficking of Wntless, endocytosis also mediates the intracellular transport of Wnts per se (Linnemannstöns et al., 2020; Witte et al., 2020). In Drosophila imaginal disc tissues, this endocytosis‐dependent Wnt trafficking inside the source cells, also known as transcytosis, has been shown to be critical for distributing extracellular Wnts as long‐range signalling molecules (Pfeiffer and Vincent, 1999; Routledge and Scholpp, 2019; Strigini and Cohen, 2000; Witte et al., 2020). After initial secretion from the apical surface of source cells, Wingless (Wg), a Drosophila Wnt, re‐enters the source cells and is trafficked through different endocytic compartments for later secretion from either the apical or basolateral side (Linnemannstöns et al., 2020; Pfeiffer et al., 2002; Pfeiffer and Vincent, 1999; Yamazaki et al., 2016; Zhu and Scott, 2004) (Figure 2).…”

“…Reggie‐1/Flotillin‐2, a cytoplasmic element of non‐caveolin lipid microdomains, had been proposed to work with Dly to facilitate Wg transcytosis (Katanaev et al., 2008). Other important regulators of Wg intracellular trafficking in the source cells include the Ykt6 v‐SNARE, which mediates endosomal trafficking of Wg endocytosed from the apical surface, and Klp98A, a kinesin family motor that facilitates the maturation and subsequent trafficking of apical endosomes containing Wg (Linnemannstöns et al., 2020; Witte et al., 2020). A similar role in regulating extracellular Wnt distribution from the source cells had been proposed for retromers in C. elegans , although the exact mechanisms remain unknown (Coudreuse et al., 2006).…”

Transcytosis in the development and morphogenesis of epithelial tissues

“…In the wing imaginal disk, a precursor epithelium from which the wing develops, a subset of cells express and secrete Wg, generating a signaling gradient across the tissue (Cadigan, 2002). Several studies have suggested that, in producing cells, Wg is secreted apically, reabsorbed by endocytosis, and then transcytosed to the basal surface of the epithelium for secondary release and signaling (Fig 5A) (Gallet et al, 2008;Yamazaki et al, 2016;Routledge & Scholpp, 2019;Witte et al, 2020). Time course imaging of tagged, inducible Wg protein supports an apical-to-basal transcytosis model (Yamazaki et al, 2016).…”