## 3 Molecular Actors in Vesicle Targeting and Fusion at the Golgi  
The fusion of transported COPI vesicles at the target Golgi membrane requires the orchestrated action of Rab GTPases, tethering complexes and SNARE proteins [20; 35; 36; 37]. Small Rab GTPases are important molecular regulators of multiple vesicle trafficking steps [38]. There are about 20 different Rab proteins that associate with the Golgi membranes [36]. In the GTP-bound active state (membrane-associated), Rab proteins recruit molecular motors and tethering factors to specific membrane domains to promote vesicle fusion [39]. Prior to fusion, transport vesicles and their cognate target membranes must be properly aligned, a process known as tethering. The tethering of vesicles at the cognate target membrane is regulated by large coiled-coil tethers (CCTs, [40; 41; 42; 43; 44]) or multisubunit tethering complexes (MTC; [35; 45]). CCTs that localize at the Golgi apparatus are named \"golgins\" [43]. In humans, there are 11 golgins including GM130, Golgi-45, Golgi-97. Golgins are anchored to the Golgi membranes by the carboxy-terminus, and protrude into the cytoplasm to capture vesicles, usually through the amino-terminus of the protein [40]. These tethers are large dimeric proteins displaying two globular heads connected by a long coiled-coil structure, which greatly facilitate the first contact with the vesicles over distances of more than 200 nm [35]. Golgins can occupy several locations within the Golgi, residing at the _cis_-Golgi, the rims of the Golgi stacks and the _trans_-Golgi network. Due to their ability to selectively tether vesicles of specific cargo content, these proteins play an essential role in directing vesicle trafficking within the Golgi. Most golgins have been found to cooperate with several trafficking players including Rab proteins and other GTPases, MTCs and SNAREs [46]. Rabs bind the coiled-coil regions within the golgin protein, whereas small Arf GTPases interact with GRAB/GRIP domains, located in the terminus of many golgins [36]. The multisubunit tethering complexes (MTCs), consisting of three to ten subunits and an overall molecular weight of 250-800 kDa, can associate with vesicles over much shorter distances comparedto CCTs [45]. Recent structural studies and sequence comparisons have led researchers to group MTCs into CATCHRs and non-CATCHRs [47]. The family of complexes associated with tethering containing helical rods (CATCHR) include DSL1/ZW10 complex, Conserved Oligomeric Golgi (COG), GARP (Golgi associated retrograde complex) and the exocyst [45]. The non-CATCHR group includes two complexes involved in regulating vesicle transport from late Golgi to endosomal/lysosomal compartments named Homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET) [45]. The multisubunit Transport Particle (TRAPP) complexes (I, II and III) have been classified as MTCs with a unique structure [48]. TRAPPI function is involved in ER-Golgi transport [49]. Although MTCs and CCTs function as tethers, they are implicated in different steps of vesicular tethering [50]. The long CCTs are required for the initial capturing of distant vesicles through transient and low affinity interactions. Conversely MTCs, which can bind vesicles at short distances from the target membrane, act in later events of tethering and facilitate SNAREpin in assembly. Thanks to their multiple subunit structures, MTCs can simultaneously interact with various vesicle trafficking regulators (i.e., CCTs, Rab1 and SNAREs), playing a key role in coordinating vesicular tethering with docking and fusion [35]. The fusion of the uncoated vesicle with the target membrane at the Golgi requires the assembly of functional SNAREs (soluble \(N\)-ethylmaleimide-sensitive factor activating protein receptors) complexes [50]. SNARE proteins share a characteristic coiled-coil motif of approximately 70 amino acids comprising heptad repeats, and can localize on either the target (t-SNARE) or the vesicle membrane (v-SNARE).