Differential roles of syntaxin 7 and syntaxin 8 in endosomal trafficking

To understand molecular mechanisms that regulate the intricate and dynamic organization of the endosomal compartment, it is important to establish the morphology, molecular composition, and functions of the different organell es involved in endosomal trafficking. Syntaxins and vesicle-associated memb rane protein (VAMP) families, also known as soluble N-ethylmaleimide-sensit ive factor (NSF) attachment protein receptors (SNAREs), have been implicate d in mediating membrane fusion and may play a role in determining the speci ficity of vesicular trafficking;Although several SNAREs, including VAMP3/ce llubrevin, VAMP8/endobrevin, syntaxin 13, and syntaxin 7, have been localiz ed to the endosomal membranes, their precise localization, biochemical inte ractions, and function remain unclear. Furthermore, little is known about S NAREs involved in lysosomal trafficking. So far, only one SNARE, VAMP7, has been localized to late endosomes (LEs), where it is proposed to mediate tr afficking of epidermal growth factor receptor to LEs and lysosomes. Here we characterize the localization and function of two additional endosomal syn taxins, syntaxins 7 and 8, and propose that they mediate distinct steps of endosomal protein trafficking. Both syntaxins are found in SNARE complexes that are dissociated by alpha-soluble NSF attachment protein and NSF. Synta xin 7 is mainly localized to vacuolar early endosomes (EEs) and may be invo lved in protein trafficking from the plasma membrane to the EE as well as i n homotypic fusion of endocytic organelles. In contrast, syntaxin 8 is like ly to function in clathrin-independent vesicular transport and membrane fus ion events necessary for protein transport from EEs to LEs.