Abstract
Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface. While the release and anterograde movement of Golgi-derived vesicles require the small GTPase RAB6, its effector ELKS promotes the targeting and docking of secretory vesicles to particular areas of the plasma membrane. Here, we show that specialized cell types exploit and divert the secretory pathway towards lysosome related organelles. In cultured melanocytes, the secretory route relies on RAB6 and ELKS to directly transport and dock Golgi-derived carriers to melanosomes. By delivering specific cargos, such as MART-1 and TYRP2/ DCT, the RAB6/ELKS-dependent secretory pathway controls the formation and maturation of melanosomes but also pigment synthesis. In addition, pigmentation defects are observed in RAB6 KO mice. Our data together reveal for the first time that the secretory pathway can be directed towards intracellular organelles of endosomal origin to ensure their biogenesis and function.
Highlights
Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface
Immunofluorescence microscopy (IFM) showed that endogenous RAB6 localized to the Golgi apparatus and trans-Golgi network (TGN) and to scattered vesicles tightly apposed to TYRP1 and melanin containing melanosomes (Fig. 1a,b and Supplementary Fig. 1a, arrows)
We reveal that pigment cells redirect the RAB6 secretory pathway towards their lysosome-related organelles (LROs) and exploit this novel Golgi-to-LRO route for the biogenesis of melanosomes and the pigmentation process
Summary
Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface. Once newly synthesized proteins reach the Golgi apparatus, they can exit at the trans-Golgi network (TGN) by sorting into different carriers and transport to various destinations (for example, endosomes, plasma membrane)[1]. Whereas RAB6 controls the microtubule-dependent anterograde transport of exocytic carriers, ELKS promotes the docking and contributes to the fusion of those vesicles with active zones of the plasma membrane[6] that manifests in a subset of cell types like inhibitory neurons[16,17]. Melanogenic enzymes (Tyrosinase (TYR) and related proteins (TYRP1 and TYRP2/ DCT)) initiate synthesis of melanins in stage-III, which fill the lumen of stage-IV; on the other hand, structural proteins like PMEL and MART-1 contribute to the morphology and homoeostasis of melanosomes[19] Before reaching melanosomes, these neo-synthesized components are sorted at the Golgi and packaged into derived vesicles. Molecular machineries involved in cargo recognition, sorting, transport and delivery from Golgi are unknown
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