Module 4 · Cell-Cycle Biology
Golgi Disassembly in Mitosis
The mammalian Golgi ribbon disassembles at the onset of mitosis and reassembles in each daughter cell in telophase. Disassembly involves disconnection of cisternae, loss of cisternal stacking, and dispersal into small vesicular and membrane clusters called Golgi haze or mitotic Golgi fragments. The mechanism — and the existence of a “Golgi mitotic checkpoint” — has been worked out over the past two decades.
1. Why Disassemble?
The mitotic cell partitions every organelle between daughter cells. For some (nucleus: always disassembled in open mitosis; ER: disperses as a tubular network) this is through structural reorganisation; for others (mitochondria: duplicate in advance and randomly distribute) through numerical expansion. The Golgi could in principle be duplicated and distributed as intact stacks, but mammalian cells dissolve the ribbon into ~200 small clusters that are then stochastically partitioned. Why?
Two hypotheses: (i) ribbon disassembly is required to release Golgi-associated factors (including PLC, Src-family kinases, small GTPases) that the cell needs elsewhere in mitosis; (ii) smaller fragments partition more equitably by simple diffusion than one large ribbon would.
2. Triggering Signals
Disassembly proceeds in two steps:
- Ribbon unlinking (G2/M): phosphorylation of GRASP65 (CDK1, Plk1, MEK1) disrupts GRASP dimerisation, separating cisternal stacks from one another. Proceeds in late G2; essential for mitotic entry. Cells with non-phosphorylatable GRASP65 mutants arrest at G2/M (Sutterlin 2002; Feinstein & Linstedt 2007). This is the “Golgi mitotic checkpoint.”
- Cisternal disassembly (prophase/metaphase): phosphorylation of GRASP55, GRASP65, golgins, and matrix proteins disperses individual stacks into vesicles. COPI cage disassembly contributes; the proportion mediated by continued budding vs active fragmentation is still debated.
CDK1-cyclin B and Plk1 are the dominant kinases; MEK1/ERK2 contributes. Dephosphorylation by phosphatases (PP2A) drives reassembly in telophase.
3. Reassembly in Telophase
As cyclin B is destroyed at the metaphase-to-anaphase transition and CDK1 activity drops, PP2A dephosphorylates GRASPs and Golgi resident proteins. Membrane fragments fuse to reform cisternae; GRASP dimers restack them; the centrosome reorganises the microtubule cytoskeleton to re-cluster them into a perinuclear ribbon. The entire reassembly proceeds in ~30–45 minutes in cultured cells.
4. Golgi Stress Response
Beyond mitosis, the Golgi is disrupted by many stressors: oxidative damage, monensin (H+/K+ ionophore, collapses Golgi pH), nocodazole (microtubule depolymerisation), ilimaquinone (unknown target, dramatic dispersal). Recent work (Yoshida 2017, Taniguchi 2019) has identified a Golgi stress response analogous to the ER UPR: specific transcription factors (TFE3, CREB3, HSP47) are activated on Golgi disruption and upregulate genes restoring Golgi capacity. This is a young field but a compelling parallel to the ER UPR (see theER UPR module).
5. Golgi Stress in Neurodegeneration
Golgi fragmentation is observed in Alzheimer’s, Parkinson’s, ALS, and Huntington’s disease brain tissue. In ALS motor neurons, TDP-43 aggregates appear to sequester Golgi components, disrupting axonal transport. In α-synuclein-accumulating Parkinson’s models, Golgi is compromised before dopaminergic-neuron loss. Whether Golgi disassembly is cause or consequence of neurodegeneration is still debated; therapeutic stabilisers of Golgi structure are in preclinical development.