As discussed previously, newly formed vesicles that bud off from the donor membrane (such as cell membrane or Golgi cisternae) can fuse with a number of possible target membranes within the cell. Shortly after budding and shedding its clathrin coat, a vesicle must be targeted to the appropriate cellular compartment. A targeting mechanism can be likened to a taxi driver in a large city who successfully delivers a passenger to the proper street address. In the cell, the street address is recognized by Rab-GTPase bound to the membrane of the traveling vesicle. Rab-GTPase interacts with tethering proteins located on the target membrane. This initial interaction provides recognition of the vesicle and recruits the necessary number of tethering proteins to dock the incoming vesicle. The docking complex between Rab-GT-Pase and its receptor immobilizes the vesicle near the target membrane (Fig. 2.14). To ensure accurate targeting, each vesicle contains a vesicle-specifc membrane protein called a v-SNARE. The target membrane also contains a specific membrane protein, t-SNARE, that interacts with v-SNARE to form the cis-SNARE complex. SNAREs are a family of transmembrane proteins that were originally grouped according to their location within the vesicle (v-SNARE) or target membrane (t-SNARE). They guarantee the specificity of interaction between a  particular vesicle and its target membrane and also promote membrane fusion that follows immediately after the cis-SNARE complexes are formed. After fusion, the SNARE complexes are dismantled with the help of the NSF/ -SNAP protein complex and recycled for use in another round of vesicle fusion.
FIGURE 2.12 • Photomicrograph of secretory cells of the pancreas. Note that secretory vesicles containing protein ready for secretion fll the apical portion of the cells. This process re-quires an external signaling mechanism for the cell to discharge the accumulated granules. 860.
The TEM reveals the presence in the cytoplasm of membrane-enclosed compartments associated with all the endocytotic pathways described above (Fig. 2.15). These compartments, called early endosomes, are restricted to a portion of the
FIGURE 2.13 • Diagram showing two pathways for exocytosis. Newly synthesized proteins are synthesized in the rough endoplasmic reticulum (rER). After their initial post-translational modifcation, they are delivered in COP-II–coated vesicles to the Golgi apparatus. After additional modifcation in the Golgi apparatus, sorting, and packaging, the fnal secretory product is transported to the plasma membrane in vesicles that form from the trans-Golgi network (TGN). Note that retrograde transport is present between Golgi cisternae and is mediated by the COP-I–coated vesicle. Two distinct pathways are recognized. Blue arrows indicate the constitutive pathway in which proteins leave the cell immediately after their synthesis. In cells using this pathway, almost no secretory product accumulates, and thus few secretory vesicles are present in the cytoplasm. Red arrows indicate the regulated secretory pathway in which protein secretion is regulated by hormonal or neural stimuli. In cells using this pathway, such as the pancreatic acinar cells in Figure 2.12, secretory proteins are concentrated and transiently stored in secretory vesicles within the cytoplasm. After appropriate stimulation, the secretory vesicles fuse with the plasma membrane and discharge their contents.
cytoplasm near the cell membrane where vesicles originating from the cell membrane fuse. From here, many vesicles return to the plasma membrane. However, large numbers of vesicles originating in early endosomes travel to deeper structures in the cytoplasm called late endosomes. The latter typically mature into lysosomes.