# 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
In ACG1A and ODCD, Golgi disruption impairs the posttranslational processing and secretion of several extracellular matrix (ECM) components [64]. A mouse model bearing a nonsense mutation in TPIP11 with a complete loss of GMAP-210 resulted in ACG1A with fetuses showing an absence of mineralization. This affected chondrocyte differentiation, made them apoptotic, and reduced ECM production. Detailed analysis of cellular defects in the chondrocytes and osteoblasts revealed ER stress, vesicle aggregation and abnormal Golgi morphology. Studies on the glycosylation status in TRIP11 mutant mice fibroblasts using lectin staining confirmed incomplete glycan processing in the Golgi. Proteoglycan synthesis also differed in the mutant chondrocytes. The same study also investigated a 27-week-old human fetus with lethal ACG1A and found a similar phenotype as they did in their mouse model [63]. In hypomorphic mutations in TRIP11 causing ODCD, the milder counterpart of ACG1A, patient fibroblasts showed some degree of Golgi-localized GMAP210, which was completely absent in the ACG1A patient's and the Golgi morphology was mostly normal. Patient fibroblasts also secreted reduced levels of ECM proteins. Both ACG1A and ODCD causing TRIP11 mutations have similar negative effects on glycosylation and proteoglycan modification of the ECM component decorin [64]. GOLGA3 (Golgin 160): Like GMAP210, Golgin160 is also localized to the _cis_-Golgi and functions in Golgi positioning and structure. It recruits the microtubule motor dynein to the Golgi [59; 68]. Similar to the GMAP210 KD effects in HeLa cells, siRNA-induced KD of Golgi160 in the same cell line resulted in Golgi fragmentation and the dispersal of Golgi mini stacks [59]. A missense mutation in GOLGA3 has been linked to autism [69]. USOI (p115): p115 belongs to the golgin family of tethers. It is involved in transport between ER and Golgi. At the _cis_-Golgi it interacts with the golgins, GM130 and Giantin as well as the SNAREs, BET1 and Sec22b [70; 71; 72]. The golgin, p115, was discovered as a protein that stimulated the proper glycosylation of the cargo protein VSVG in the in vitro intra-Golgi trafficking setup [73]. It was later shown to play an important role in the formation of pre-Golgi ERGIC intermediates [74]. Early studies suggested that p115 is recruited by Rab1 to COPII vesicles budding from the ER where it interacts with COPII vesicle-associated SNAREs [75]. It interacts with the STX5 SNARE partners GOSR1/BETIL/YKT6 and GOSR2/BET1/Sec22b [76] and p115 is essential for cisternal stacking and cisternal growth, facilitating the initial tethering of Golgi cisternae [77]. Moreover, it has a vital role in the biogenesis and maintenance of the Golgi as it interacts with the COG complex and participates in vesicular trafficking at the Golgi [78]. Although the depletion of p115 in tissue culture cells leads to glycosylation defects [79], CDG-causing mutations have not been reported so far. GOLGB1 (Giantin): Giantin is the largest and well-characterized _cis_-golgin. It is anchored at the _cis_-Golgi by its transmembrane domain and either has a short or no luminal domain at its C-terminus [80; 81]. Regulation of the Golgi architecture is one of its key functions. Apart from p115, Giantin interacts with Rab1, Rab6, and GM130. Loss of Giantin can accelerate the anterograde transport instead of blocking it [7; 81; 82; 83; 84]. While Giantin may be dispensable in maintaining Golgi structure, its depletion inhibits lateral tethering between the cisternae [83; 84]. GOLGB1 loss-of-function zebrafish [82] and mouse [85] models revealed that Giantin has specific functions in protein glycosylation and tissue morphogenesis. The expression of Golgi-resident glycosyltransferases like GALNT3 is altered due to a loss of Giantin [82]. GOLGA5 (Golgin-84): Human golgin-84 is well conserved in evolution with orthologs in plants, but not fungi.