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Cell cycle-regulated Golgi stack assembly and function
Yanzhuang Wang 1 , Yi Xiang 1 , Danming Tang 1 .
University of Michigan, Ann Arbor 1
Abstract:
The unique structure of the Golgi in almost all eukaryotic cells is a stack of flattened cisternal
membranes, but how this structure is formed at the molecular level and why its formation is
important for cellular functions remain elusive. We have developed an in vitro system to
reconstitute the process of mitotic Golgi disassembly and post-mitotic reassembly in
mammalian cells, which allowed us to reveal the molecular mechanism of the Golgi biogenesis
during the cell division. Mitotic Golgi fragmentation involves membrane vesiculation coupled
with cisternal unstacking; post-mitotic Golgi reassembly is mediated by membrane fusion to
form single cisternae and by stack formation. Stack formation directly involves the Golgi
stacking protein GRASP65 and GRASP55, which play complementary and essential roles in
Golgi cisternal stacking by forming mitotically regulated trans-oligomers. By inhibition of
GRASP65/55 oligomerization we are able to manipulate Golgi stack formation and thus
determine the biological significance of stacking. We demonstrate that Golgi cisternal
unstacking stimulates COPI vesicle budding and thus enhances protein transport. Golgi
fragmentation, however, impairs glycosylation of cell surface proteins and reduces cell adhesion.
Inhibition of Golgi disassembly at the onset of mitosis also affects cell cycle progression. We
propose that Golgi stack formation is a flux regulator for protein trafficking and thereby
maintain the quality of protein glycosylation. Structural and functional Golgi defects in disease
models are explored in this study.