Researchers at the University of California, Santa Barbara have recently made new discoveries regarding a specific protein and its effects on cytokinesis, the final step of cell division.
A new study conducted in the laboratory of Molecular, Cellular, and Developmental Biology (MCDB) associate professor Zach Ma revealed a function for WDR5, a protein known for its role in gene expression, where information encoded in genes is converted to products such as ribonucleic acid (RNA) and protein. WDR5 is a subunit of a five-protein complex, and mutations in members of the complex can result in leukemia or other disorders affecting organs in the body.
Certain proteins act as managers and have a wide variety of processes that determine the fate of a cell. One group of proteins is called the WD-repeat (WDR) family, which functions to help a cell choose which of the possible gene products it will make.
“The WDR proteins all have different functions, but are grouped together because they all fold into a three-dimensional structure resembling a doughnut,” said lead author Jeff Bailey, a graduate student in UCSB’s MCDB department. “This conformation allows the WDR proteins to be a stable platform on which protein complexes assemble or disassemble.”
When the body makes new cells, it divides into different cells via cytokinesis. When a stem cell divides to produce a differentiated type of cell, such as a skin cell or a neuron, stem cells retain the midbody while differentiated cells do not.
“Because only the stem cell retains the midbody, this suggested that the midbody had important functions,” said Bailey. “When the midbody isn’t cut correctly, the cell can refuse and create one cell with two nuclei, which is thought to be part of what happens when a tumor forms.”
The work involved the fusion of WDR5 to a green fluorescent protein molecule called EGFP. The fluorescence of EGFP allowed researchers to detect WDR5 in its location during cytokinesis.
“When we used EGFP, it showed that there were some dots between the two nuclei,” said Bailey. “It was really unexpected so we looked further into it and saw that it was WDR5 in a part of the midbody called the dark zone. The presence of WDR5 outside the cell nucleus led us to believe that it had a role in cell division.”
Scientists found that the protein localized in the midbody and contributed to abscission, the separation of two daughter cells at the completion of cytokinesis. WDR5 promotes the disassembly of midbody microtubules, the major structural components of the midbody that must be cleared before abscission can occur.
When researchers artificially reduced the amount of WDR5 in cells, cytokinesis was delayed and more cells failed to divide. “When there is less WDR5 in cells, it takes longer for the cell to divide,” said Bailey. “For example, with WDR5, it could take a cell about an hour to divide. However, with less WDR5, the cell could take several hours to divide or not divide at all.”
A single protein can perform several distinct functions depending on its location within the cell, making it difficult to study one function without disrupting the others. However, with the help of previous structural studies, the UCSB team identified surfaces of the WDR5 “doughnut” may be the reason for its role in cell division.
“We have a better idea on the role of WDR5 in cytokinesis,” said Bailey. “This could help us better understand the different physiological and pathological events related in the process of cell division.