Nav: Home

Illuminating the dark zone

April 29, 2015

The human body is a cross between a factory and a construction zone -- at least on the cellular level. Certain proteins act as project managers, which direct a wide variety of processes and determine the fate of the cell as a whole.

One group of proteins called the WD-repeat (WDR) family helps a cell choose which of the thousands of possible gene products it should manufacture. These WDR proteins fold into a three-dimensional structure resembling a doughnut -- an unusual shape that allows WDR proteins to act as stable platforms on which large protein complexes can assemble or disassemble.

A new study conducted by scientists at UC Santa Barbara reveals a novel function for WDR5, a protein known for its critical role in gene expression whereby information encoded in genes is converted into products like RNA (ribonucleic acid) and protein. In cells, WDR5 is a subunit of a five-protein complex. Mutations in members of this complex can result in childhood leukemia and other disorders affecting numerous organ systems in the body. The UCSB team worked with WDR5 in cultured human cell lines. The results of the study appear in the Journal of Biological Chemistry.

"We found that when two cells divide, WDR5 is localized to a very interesting cellular structure called the midbody," said lead author Jeff Bailey, a graduate student in UCSB's Department of Molecular, Cellular and Developmental Biology (MCDB). "In the past, although associated with cell division, the midbody was considered 'junk,' but that has changed in the last decade. Now the midbody is believed to be important during stem cell differentiation."

When a stem cell divides to produce a differentiated type of cell like a skin cell or a neuron, stem cells retain the midbody while differentiated cells do not. "This suggests that the midbody has important functions," Bailey explained. "Also, when the midbody isn't cut correctly, the cells can re-fuse, creating one cell with two nuclei. This is thought to be part of what happens when a tumor forms."

Conducted in the laboratory of MCDB associate professor Zach Ma, this new work involved the fusion of WDR5 to a green fluorescent protein molecule called EGFP. Although dense material within the midbody thwarts conventional methods of protein detection, the fluorescence of EGFP tethered to WDR5 revealed its location during cell division, or cytokinesis.

The researchers were surprised to find WDR5 in a part of the midbody called the dark zone. "It was very unexpected," Bailey said. "The presence of WDR5 outside the cell nucleus gave us a clue about its function, which we tested," Ma added.

The scientists found that not only did the protein localize in the midbody, it also contributed to abscission, the separation of two daughter cells at the completion of cytokinesis. In addition, WDR5 promotes the disassembly of midbody microtubules, the major structural components of the midbody that must be cleared before abscission can occur.

When the investigators artificially reduced the amount of WDR5 in cells, cytokinesis was substantially delayed and more cells failed to divide properly. "When histology is performed on a tumor, pathologists look for cells that have two nuclei," Bailey explained. "This can indicate that cells within the tumor are failing to properly finish cytokinesis."

Because a single protein can perform several distinct functions according to its location within a cell, it can be challenging to study one function without disrupting the others. Guided by previous structural studies, however, the UCSB team identified surfaces of the WDR5 "doughnut" that may be specific to its role in cell division.

"We have shed some light on the role of WDR5 in cytokinesis," Ma said, "which may in turn help us better understand the diverse array of physiological as well as pathological events related to malfunction of these proteins in the process of cell division."
-end-


University of California - Santa Barbara

Related Cell Division Articles:

Discovery of a novel chromosome segregation mechanism during cell division
When cells divide, chromosomes need to be evenly segregated. This equal distribution is important to accurately pass genetic information to the next generation.
Researchers identify earliest known protein needed for cell division
Researchers from three US universities have identified, using roundworms, the earliest-acting protein known to duplicate the centriole, a tiny cylinder-shaped structure that is a key component of the machinery that organizes cell division in animals.
Study finds new target for controlling cell division
Modern genome sequencing methods used to measure the efficiency of synthesis of individual protein during cell division has found that the enzymes that make lipids and membranes were synthesized at much greater efficiency when a cell is ready to split.
Calcium aids chromosome condensation prior to cell division
Research led by the University of Osaka found that calcium ions help maintain the structure of chromosomes during mitosis by promoting their condensation.
Live cell imaging of asymmetric cell division in fertilized plant cells
Plant biologists have succeeded for the first time in visualizing how egg cells in plants divides unequally (asymmetric cell division) after being fertilized.
Three rings stop cell division in plants
Arising from a collaboration between plant and animal biologists, and organic chemists at ITbM, Nagoya University, the group succeeded in developing a new compound, a triarylmethane that can rapidly inhibit cell division in plants.
Strong, steady forces at work during cell division
Biologists who study the mechanics of cell division have for years disagreed about how much force is at work when the cell's molecular engines are lining chromosomes up in the cell, preparing to winch copies to opposite poles across a bridge-like structure called the kinetochore to form two new cells.
Unconventional cell division in the Caribbean Sea
Bacteria are immortal as long as they keep dividing. For decades it has been assumed that a continuous, proteinaceous ring is necessary to drive the division of most microorganisms.
Differing duration of brain stem cell division
Stem cells in the developing human brain take more time to arrange the chromosomes before distribution than stem cells of great apes.
Cell division and inflammatory disease link revealed
A ground-breaking study by University of Manchester and Liverpool scientists and published in the journal eLife has identified a new link between inflammation and cell division.

Related Cell Division Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".