Figure 10. Model for Ptc traffic and basal exocytosis.

1. We propose a sorting mechanism that redirects Ptc to the basal membrane for its presentation for Hh reception in the cytonemes of receiving cells. In black numbers and arrows we show the vesicle‐sorting route for Ptc presentation at the basal plasma membrane, (1) endocytosis of Ptc from apical membranes, (2) late endosome structures to form MVBs that (3) fuse to the basal plasma membranes exposing Ptc for Hh reception. In red numbers and arrows, we show the parallel vesicle‐sorting route directing Hh/Ptc degradation after (1) reception and (2) endocytosis at basal membranes, towards (3) MVB formation for degradation at lysosomes. This novel mechanism for polarized Ptc trafficking requires components of the ESCRT machinery (MVB‐mediated processes such as recycling), the Tetraspanin proteins (to define MVB and EV membrane domains) and the SNARE proteins (to regulate vesicle fusion). Potential mechanisms for the transport within cytonemes of two vesicle types, for Ptc membrane deposition and post‐reception, are not shown in the model as they are still unexplored.
2. Schematic view of the effect over Hh signalling after transient inhibition of the MVB‐mediated recycling and fusion process proposed for Ptc localization at basal membranes. Top panel shows Hh dispersion in a wild‐type situation, while bottom panel shows an extended dispersion after transient conditions that reduce Ptc basal membrane exposure and thus decrease Hh reception, flattening the signalling gradient.