the cell surface area, will be likely to use motor proteins and a cytoskeletal track to get closer to their target. Before tethering would have been appropriate, many of the proteins used for the active transport would have been instead set for passive transport, because the Golgi apparatus does not require ATP to transport proteins. Both the actin- and the microtubule-base are implicated in these processes, along with several motor proteins. Once the vesicles reach their targets, they come into contact with tethering factors that can restrain them. Vesicle tethering It is useful to distinguish between the initial, loose tethering of vesicles to their objective from the more stable, packing interactions. Tethering involves links over distances of more than about half the diameter of a vesicle from a given membrane surface (>25 nm). Tethering interactions are likely to be involved in concentrating synaptic vesicles at the synapse. Vesicle docking Secretory vesicles transiently dock and fuse at the porosome at the cell plasma membrane, via a tight t-/v-SNARE ring complex. Vesicle priming In neuronal exocytosis, the term priming has been used to include all of the molecular rearrangements and ATP-dependent protein and lipid modifications that take place after initial docking of a synaptic vesicle but before exocytosis, such that the influx of calcium ions is all that is needed to trigger nearly instantaneous neurotransmitter release. In other cell types, whose secretion is constitutive (i.e. continuous, calcium ion independent, non-triggered) there is no priming. Vesicle fusion Transient vesicle fusion is driven by SNARE proteins, resulting in release of vesicle contents into the extracellular space (or in case of neurons in the synaptic cleft). The merging of the donor and the acceptor membranes accomplishes three tasks: The surface of the plasma membrane increases (by the surface of the fused vesicle). This is important for the regulation of cell size, e.g., during cell growth. The substances within the vesicle are released into the exterior. These might be waste products or toxins, or signaling molecules like hormones or neurotransmitters during synaptic transmission. Proteins embedded in the vesicle membrane are now part of the plasma membrane. The side of the protein that was facing the inside of the vesicle now faces the outside of the cell. This mechanism is important for the regulation of transmembrane and transporters. Vesicle retrieval Retrieval of synaptic vesicles occurs by endocytosis. Most synaptic vesicles are recycled without a full fusion into