Melanosomes are lysosome-related organelles whose biogenesis relies on the efficient delivery of melanin-synthesising enzymes from endosomes to pre-melanosomes. SNARE proteins underlie all membrane fusion events, but it is unclear which SNAREs are involved in melanosome maturation. Having previously shown that melanosomal cargo relocalises to syntaxin 13 (STX13)-positive endosomal structures when melanosomal traffic is disrupted, Subba Rao Gangi Setty and colleagues now (p. ) provide the first clear demonstration that the Qa-SNARE STX13 functions in melanosome biogenesis. STX13 localised to tubular endosomal domains in the vicinity of melanosome-protein-positive structures; STX13 also localised to melanosomes upon overexpression. By contrast, knockdown of STX13 caused loss of pigmentation in melanocytes and re-routing of melanosomal proteins to lysosomes. Furthermore, mutation of the STX13 N-terminal regulatory Habc domain increased STX13 SNARE activity and redistributed it to melanosomes, suggesting that the Habc domain regulates STX13 recycling to endosomes. Importantly, the authors found that the R-SNARE vesicle-associated membrane protein 7 (VAMP7) localised to melanosomes, and its knockdown decreased melanocyte pigmentation and melanosomal protein levels, and prevented STX13 from localising to melanosomes. Notably, VAMP7 was degraded upon STX13 depletion. Taken together, these results show that endocytic STX13 functions together with melanosomal VAMP7 to regulate melanosome cargo delivery and biogenesis.
