Golgi ribbon disassembly during mitosis, differentiation and disease progression

Abstract

The Golgi apparatus is tightly integrated into the cellular system where it plays essential roles required for a variety of cellular processes. Its vital functions include not only processing and sorting of proteins and lipids, but also serving as a signaling hub and a microtubule-organizing center. Golgi stacks in mammalian cells are interconnected into a compact ribbon in the perinuclear region. However, the ribbon can undergo distinct disassembly processes that reflect the cellular state or environmental demands and stress. For instance, its most dramatic change takes place in mitosis when the ribbon is efficiently disassembled into vesicles through a combination of ribbon unlinking, cisternal unstacking and vesiculation. Furthermore, the ribbon can also be detached and positioned at specific cellular locations to gain additional functionalities during differentiation, or fragmented to different degrees along disease progression or upon cell death. Here, we describe the major morphological alterations of Golgi ribbon disassembly under physiological and pathological conditions and discuss the underlying mechanisms that drive these changes.

Figure 1

Golgi ribbon disassembly in mitosis. (a) During interphase, the Golgi stacks are interconnected into a ribbon that is localized close to the centrosomes. In late G2, the lateral connections between stacks are severed, which unlinks the ribbon and allows progression into mitosis. The cisternae then further unstack and vesiculate. Upon partitioning with the aid of the spindle, the mitotic Golgi membranes reassemble a ribbon in both daughter cells. (b) Stages and main players in mitotic Golgi disassembly. Ribbon unlinking in late G2 requires the membrane fission protein BARS and the phosphorylation of GRASP65 and GRASP55. Once the cells entered mitosis, further phosphorylation of GRASP 65 and GRASP55 induces cisternal unstacking. Simultaneously the cisternae vesiculate due to inhibition of both vesicle tethering (mediated by phosphorylation of GM130) and heterotypic fusion (mediated by ubiquitination of the t-SNARE syntaxin 5). Meanwhile, homotypic fusion of Golgi membranes is also blocked by phosphorylation of the p97 adaptors p37 and p47 and the co-factor VCIP135.

Figure 2

Golgi stacks in proliferating and differentiated mammalian cells. (a) Golgi ribbon in fibroblasts. The stacks are laterally linked together into a continuous ribbon that localizes in the perinuclear and pericentriolar region of the cell. (b) Golgi outposts in neurons. During neuronal differentiation, some stacks detach from the somatic ribbon and relocated to dendrites. These Golgi outpost function as sites for local secretion and microtubule nucleation to regulate dendrite outgrowth. (c) Golgi stacks in muscle fibers. In skeletal muscle fibers, the ribbon is broken up into stacks. Microtubules originating from the nuclear membrane and from Golgi stacks form a grid-like network.