# Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation
## 3 Membrane Trafficking Machinery
### Tethers (MTCs and Coiled-Coil Tethers)
#### 3.1.1 Coiled-Coil Tethers  
Coiled-coil tethers are structurally similar 100-200 nm long homodimers with large globular heads. Their length extends into the cytosol enabling the long-range capture of incoming cargo carriers and brings them close to their target membrane. At the Golgi, they may also function as stacking proteins holding the cisternae together (for a more in-depth review see [49] (Figure 2). The majority of the coiled-coil tethers that reside at the Golgi are called Golgins (see Table 1 for a complete list) (Figure 2). The _cis_-Golgins (USO1 (p115), GOLGA2 (GM130), TRIP11 (GMAP210), GOLGA3 (Golgin160), and GO45 (Golgin45)), and _trans_-Golgins (GOLGA1 (Golgin97), GOLGA4 (Goglin245), GCC1 (GCC88), GCC2 (GCC185), and TMF1 (TMF)), are soluble peripheral membrane proteins. GOLGB1 (Gi  
Figure 1: Schematic outline of the steps involved in Golgi enzyme recycling: 1. Membrane budding at the donor membrane is initiated by recruitment of coat proteins which directly or indirectly interact with cargo (glycosation enzyme) 2. and 3. After budding, the coat protein partially falls off and the vesicle is captured by long coiled-coil tethers. 4. Among other interactions, MTCs interact with the SNAREs on the vesicle and target membrane, thereby facilitating SNARE alignment 5. and 6. Priming of the SNAREs and formation of the _trans_-SNARE complex leads to vesicle fusion at the target membrane and cargo delivery. antin), GOLGA5 (Golgin-84) and CUX1 (CASP) have a transmembrane domain at their carboxyl termini and localize at the rims of the Golgi stack. GORASP1 (GRASP65) and its homologue GORASP2 (GRASP55) are also Golgi matrix proteins but are not classified as Golgins due to their structural differences. GOLGA2 (GM130 or Golgin95): This protein plays an important role in the development of vertebrates and invertebrates. Targeted or global depletion of GM130 in Drosophila, zebrafish and mice have shown developmental effects in the nervous and skeletal system [50; 51; 52]. Recently, GOLGA2 KO in mice has also been implicated in liver and lung fibrosis due to increased autophagy [53]. Two cases of GOLGA2 mutations have been identified in the human population. Both cases have neuromuscular disorders, including developmental delay, muscular dystrophy, seizures and microcephaly [54; 51]. In a 2019 study, a lower level of GM130 expression was shown to cause aberrant O-glycosylation and was linked to [PERSON]'s disease, also known as IgA neuropathy [55]. Though GOLGA2 CDG causing mutations in humans have not been reported, studies from cell lines do point to the essential role of GM130 in maintaining the Golgi structure and proper glycosylation [56; 57]. TRIP11 (GMAP210): Early studies on GMAP210 point to its function in Golgi cisternal organization and positioning by anchoring microtubules at the _cis_-Golgi [58; 59]. Its role in maintaining the Golgi stacks was also confirmed in HeLa cells wherein TRIP11 KD caused  
Figure 2: Schematic outline of localization of the coiled-coil tethers and the MTCs at the Golgi. Coiled-coil tethers are depicted in red. Golgi stacking proteins GRASP55 and GRASP65 are depicted in pink. The conserved oligomeric Golgi (COG) complex is the MTC that operates at the Golgi and is depicted in green, while the (Golgi associated retrograde protein) GARP complex operates at the TGN and is depicted in purple. fragmentation and vesiculation of the Golgi [60]. It is required for proper anterograde and retrograde trafficking at the ER-Golgi interface [61]. It was also shown that GMAP210 can directly capture intra-Golgi vesicles [62]. Mutations in the thyroid hormone receptor interactor 11 (TRIP11) gene encoding the Golgi-associated microtubule-binding protein 210 (GMAP210) in the human population give rise to a lethal neonatal skeletal dysplasia termed as achondrogenesis (ACG1A) type IA or the much milder nonlethal odontochondroddysplasia (ODCD) depending on whether the mutation leads to a complete or partial loss of function [63; 64; 65; 66; 67].