FIGURE 3.
The trafficking machinery determines the fate and function of the vesicles. Neutrophils contain different types of granules and vesicles that not only differ in their cargo content but also in the trafficking molecules associated with them. Recycling endosomes contain Rab11 which along with its effector Munc13-4 regulates the translocation of the flavocytochrome b558 (Cytb558) to the plasma membrane and extracellular ROS production (a).14 Specific and gelatinase granule exocytosis is regulated by Rab27a along with its effector Munc13-4. This process regulates extracellular ROS production independently of Rab11 (b).14,30 Secretory azurophilic granules contain Rab27a which recruits its effectors JFC1 (c) 59,80 and Munc13-4 (d),59,76 sequentially, to regulate exocytosis (see also Fig. 2). Further classification of azurophilic granules arises based on the trafficking machinery associated with them. While secretory azurophilic granules containing Rab27a are able to engage in exocytosis, azurophilic granules lacking Rab27a can fuse with the phagosome in a Rab27a-independent but Munc13-4-dependent manner (e).28 The late endosomal compartment contains a tripartite complex of Munc13-4 Syntaxin 7 and VAMP8 that regulates the fusion of the late endosome with the lysosome (f).45 This fusion event subsequently regulates endosomal signaling pathways such as TLR9 signaling which relies on the proteolytic cleavage of the TLR9 receptor in the endolysosome to initiate downstream signaling events including Erk activation (g)45