Syntaxin 7 is localized to late endosome compartments, associates with Vamp 8, and is required for late endosome-lysosome fusion

Protein traffic from the cell surface or the trans-Golgi network reaches th e lysosome via a series of endosomal compartments. One of the last steps in the endocytic pathway is the fusion of late endosomes with lysosomes. This process has been reconstituted in vitro and has been shown to require NSF, alpha and gamma SNAP, and a Rab GTPase based on inhibition by Rab GDI. In Saccharomyces cerevisiae, fusion events to the lysosome-like vacuole are me diated by the syntaxin protein Vam3p, which is localized to the vacuolar me mbrane. In an effort to identify the molecular machinery that controls fusi on events to the lysosome, we searched for mammalian homologues of Vam3p. O ne such candidate is syntaxin 7. Here we show that syntaxin 7 is concentrat ed in late endosomes and lysosomes. Coimmunoprecipitation experiments show that syntaxin 7 is associated with the endosomal V-SNARE Vamp 8, which part ially colocalizes with syntaxin 7. Importantly, we show that syntaxin 7 is specifically required for the fusion of late endosomes with lysosomes in vi tro, resulting in a hybrid organelle. Together, these data identify a SNARE complex that functions in the late endocytic system of animal cells.