Golgi Ribbon Unlinking: An Organelle-Based G₂/M Checkpoint

Abstract

Cell cycle checkpoints have been associated mostly with signaling mechanisms monitoring the genetic material for abnormalities and inaccuracy in partitioning, such as DNA lesions or failure in chromosome attachment to kinetochores. However, it becomes more evident that other checkpoints are turned on by cytoplasmic events, such as the cytoskeleton organization and the organelle structure. Here, we summarize recent evidence strongly suggesting that the integrity of the Golgi ribbon and more precisely the tubules interconnecting the Golgi stacks to form this ribbon, at late G 2 /early prophase, is linked to a Golgi-related G 2 /M checkpoint. A number of kinases phosphorylating a small subset of Golgi-localized proteins have been shown to promote the G 2 -specific Golgi ribbon unlinking, allowing the cell to enter mitosis. When these kinases are inactivated or when the substrates cannot be phosphorylated, Golgi unlinking is prevented and the cells are blocked or delayed in G 2 phase.

Mitotic Golgi disassembly is required for bipolar spindle formation and mitotic progression

“…The lateral tubular connections between stacks of the Golgi ribbon are severed in late G2 (9). Interfering with this step delays progression into M phase, which has been referred to as a checkpoint that monitors the integrity of the ribbon (10,12).…”

“…Golgi disassembly is initiated in late G2 phase, when the ribbon is unlinked through severing of the lateral connections between the stacks (9). Interfering with this unlinking process, either by microinjection of antibodies against the Golgi stacking protein GRASP65 or by inhibiting the membrane fission protein CtBP1/ BARS, affects transition from G2 into M phase (10)(11)(12).…”

Signalling to and from the secretory pathway

“…It is now well established that the secretory pathway responds to endogenous signalling cascades. The best studied to date is the mitotic kinase cascade, which leads to the disassembly of the Golgi complex at metaphase Colanzi and Corda, 2007;Rabouille and Kondylis, 2007), and the fragmentation and/or disappearance of the ERES (Kano et al, 2004;Stephens, 2003;Kondylis et al, 2007).…”

Mitotic regulation of SREBP and ATF6 by separation of the Golgi and ER

“…16,17 In the first phase of Golgi disassembly, the lateral connections between the cisternae of the stacks are resolved, thus converting the Golgi ribbon into individual stacks. 18 This initial step is regulated by the mitogen-activated protein kinase (MAPK) kinase 1 (MEK1), the extracellular signal-regulated kinase (ERK) and the polo-like kinases (PLK) 1 and 3. [19][20][21][22] GRASP55, a peripheral Golgi protein required for stacking of cisternae in post mitotic cells, 23 has been identified as a mitotic target for MEK1.…”