The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks

Abstract

Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis -golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi.

Post-ER Stress Biogenesis of Golgi Is Governed by Giantin

“…While we observed the reduction of cisternal length in cells lacking giantin, these authors could not detect significant changes in this Golgi parameter. Moreover, another publication by Satoh et al [120] observed that loss of giantin elongates Golgi cisternae, contradicting their own previous observation [50]. There are several explanations for this discrepancy.…”

Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation

“…In addition to giantin, certain membrane tethering proteins, such as giantin, GRASP55, and GRASP65 ( Figure 3), are thought to regulate the rate of retrograde trafficking, likely to assure efficient recycling of glycosylation enzymes to their target Golgi compartment. RNA interference-mediated depletion of giantin in HeLa cells revealed that this causes aberrant fusion of Golgi cisternae [122]. This, in turn, caused a two-fold increase in the mobility of the glycosylation enzyme ManII as measured by fluorescence recovery after photobleaching and accelerated the trafficking of VSVG to the plasma membrane [123].…”

E-Cadherin Modulation and Inter-Cellular Trafficking in Tubular Gastric Adenocarcinoma: A High-Resolution Microscopy Pilot Study

“…There is no other morphological study yet detailing the expression of Giantin in the epithelial component of gastric carcinoma at the tissue level; however, as the Golgi vesicles suffer fragmentation and morphological changes in cancer cells, it is difficult to interpret if its detection by immunohistochemistry would also point towards a functional protein. Its exact function is not known, and very recently it has been proposed that contrary to the classical view that Giantin would promote trans-vesicle transport of maturing glycol-proteins, it might in fact result in delayed transport between stacks that may enable a correct glycosylation of proteins passing towards the membrane [ 28 ]. It is worth mentioning that none of the above-mentioned studies selected only epithelium for analysis, but rather performed quantitative studies on whole tissue without separating the stroma.…”