April 23, 2004

Yeast leads to rise in knowledge of cell division

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Kathleen Gould, Ph.D.

Yeast leads to rise in knowledge of cell division

A new study by a Vanderbilt University Medical Center research team drafts a blueprint for the cellular machinery that directs the division of one cell into two.

Each day in the human body, new cells are being created by the process of cell division (mitosis).

For example, as a cut on your finger heals, two new “daughter” skin cells are born from a single “mother” cell to replace the damaged ones.

If one had a microscope powerful enough to see the molecular events going on within the dividing cell, one could observe a cluster of molecules congregating at tiny structures at the poles of the nucleus. The structures would appear to be towing the original cell’s DNA in opposite directions to make the two new cells.

In the yeast cell, those structures, called spindle pole bodies, have a number of proteins attached to them. Together, this network of proteins is called the septation initiation network. This network coordinates cytokinesis — the division of the cell’s cytoplasm between the two new cells — and the division of the nucleus, which houses the chromosomes that contain the cell’s genetic material.

“One of the major interests of the lab is to understand how cytokinesis is coordinated with nuclear division so that chromosomes are segregated equally to two daughter cells,” said Kathleen Gould, Ph.D., professor in the Department of Cell and Developmental Biology at Vanderbilt and Howard Hughes Medical Institute Investigator. “If that process is uncoordinated, cytokinesis could occur prior to complete chromosome segregation, and that would be disastrous for the cell.

“Over the years, we’ve been piecing together this pathway through genetics and biochemistry. Now we think we have an overall picture of how this network is organized,” Gould said.

In the new study, which appeared in the April 6 issue of Current Biology, Gould and colleagues describe how the components of the septation initiation network are assembled into a cohesive framework, and identify the location of the network within the yeast cell.

The researchers found that two proteins, Sid4p and Cdc11p, are permanent members of the spindle pole body. These proteins provide a molecular “scaffold” for the multitude of transient regulatory proteins to attach to the spindle pole body.

“One of the interesting aspects of the work is that the pathway is organized at the spindle poles rather than at the site of cell division, and that puts it in the perfect position to coordinate signals governing nuclear division with those involved in cell division,” said Gould.

Although yeast may rank low on the evolutionary ladder, they provide an ideal model to study this process.

“The events of mitosis are very easy to discern in this yeast and the factors that are essential in this yeast are the same as those that are essential in animal cells,” Gould said.

Gould explained that since this network is likely to be similar between yeast and animal cells, it provides a starting point for researchers to identify the important regulating cell division in higher organisms.

“Certain components of this pathway have been identified in cells from higher organisms, and we feel strongly that the whole pathway is there, but we haven’t put it together yet,” she said.

Since a number of important questions remain to be addressed. Gould’s lab continues to probe the yeast’s molecular machinery to address how the pathway gets turned on and off at the appropriate times.

Gould will continue to dissect the details of pathway regulation, which could provide insight into what happens when this system malfunctions — possibly improving the understanding of processes like cell death and cancer.

Other authors of the paper include Jennifer Morrell, Gregory Tomlin, Srinivas Venkatram, Anna Feoktistova, Joseph Tasto, and Sapna Mehta of the Department of Cell and Developmental Biology; Jennifer Jennings and Andrew Link of the Department of Microbiology and Immunology; Srividya Rajagopalan and Mohan Balasubramanian of the National University of Singapore.

The research was supported by the Howard Hughes Medical Institute.