University of Michigan molecular biologists have learned how cells generate a new Golgi during cell division. The Golgi is a cellular structure with the important role of sending molecules to the right places inside and outside of the cell. The Golgi is analogous to “the post office” within the cell, explains Yanzhuang Wang, professor of molecular, cellular and developmental biology, and principal investigator of the research group that made the discovery. "Because Golgi function is important for normal cellular activities, eventually every cell needs a Golgi to live, " he says. This discovery, just published in Developmental Cell, helps decode the molecular mechanism that controls Golgi duplication in dividing cells and also contributes to the understanding of the Golgi dysfunction-related human diseases.
In addition to its important function, the Golgi has perhaps the most beautiful membrane architecture in the cell, says Wang. Its basic structure is 5 to 6 flat membrane discs that are closely aligned into a stack, like you overlay a number of pancakes into a stack. It is necessary to understand how the stacked structure of the Golgi is formed and why its formation is important for Golgi function. "It is even more fascinating to know how the cell generates a new Golgi during cell division," he adds.
Cells cannot generate a new Golgi from scratch. Instead, a cell disassembles the Golgi into small membranous pieces when the cell starts to divide, and reassembles them into a new Golgi in each daughter cell in the later stages of cell division. For many years, little was known on how the Golgi disassembly and reassembly process is controlled at the molecular level.
The researchers have created a novel method to observe Golgi breakdown and reformation in a test tube. They can control Golgi breakdown and reformation by manually adding proteins isolated from normal growing cells and dividing cells. This new approach allowed them to discover the molecular machineries that control Golgi replication. One breakthrough they have made is that ubiquitin regulates this disassembly and reassembly process of the Golgi.
Ubiquitin is a small protein that is often associated with protein degradation in the cell. However, in the Golgi, ubiquitin is a signal that is required for the assembly of the Golgi structure in newly divided cells. When cells start to duplicate and split, an ubiquitin molecule is added onto a Golgi membrane protein, interfering with the Golgi integrity and breaking down the Golgi membrane structure. Subsequently, in the duplicated new cells, the ubiquitin molecule is removed from this Golgi protein, and so the small pieces of Golgi membranes can be fused to reform a new Golgi. The Wang group had previously identified the enzymes that attach and remove ubiquitin to membrane substrates in the cell cycle, and now they have found the target on the Golgi membranes.
Shijiao Huang, a research fellow in Wang's lab, is the lead author on the paper, Monoubiquitination of Syntaxin 5 Regulates Golgi Membrane Dynamics during the Cell Cycle