Organisms precisely regulate cell size to ensure that daughter cells have sufficient cellular material to thrive or to create specific cell types: a tiny sperm versus a gargantuan egg for example.
In single-celled organisms such as yeast and bacteria nutrient availability is the primary determinant of cell size. In animal cells size is controlled in large part by a molecule that senses the blood sugar dependent hormone insulin.
Petra Levin, Ph.D., Assistant Professor of Biology at Washington University in St. Louis, and her laboratory have recently identified a trio of enzymes that act in concert to link nutrient availability to cell size in the soil bacterium Bacillus subtilis.
Levin and her lab are looking into the factors that control the timing and position of cell division in B. subtilis. B. subtilis serves as the model system for a large family of bacteria that includes the causative agents of several important diseases, including anthrax and botulism. By learning how these simple organisms regulate division, we can better understand why this process goes awry in cancer cells resulting in uncontrolled growth and aberrant division.
A primary focus of the Levin lab's research is a protein called FtsZ. FtsZ is an ancestor of tubulin, the protein that is responsible for distributing duplicated chromosomes between dividing human cells. In bacteria, FtsZ forms a ring at the future division site. The FtsZ ring then recruits all other components necessary for cell division and serves as the scaffolding for the entire division process.
The factors that regulate FtsZ ring formation determine when and where the cell is going to divide. "Theoretically a cell could divide anywhere and at anytime," said Brad Weart, a graduate student in Levin's lab. "The cell has to very precisely restrain that process so that it only happens when and where the cell wants it to happen."
In their most recent paper, published in the July 27, 2007 issue of Cell, Weart et al. identified a metabolic sensor that links cell division and cell size in B. subtilis with nutritional availability. This sensor is comprised of a three enzyme pathway that was previously shown to be involved in synthesizing a modified component of the cell membrane. The Levin lab's data indicates the pathway also has a major role in cell division. "So far this has been the only pathway that's been identified in bacteria that directly regulates cell size," says Levin.
Typically, cells in nutrient-rich environments grow bigger than cells in nutrient-poor environments. The Levin lab determined that mutations in genes encoding the three enzymes resulted in cells that were small even when they were in a nutrient-rich environment. "Basically, the cells had no way to tell the division apparatus to wait until they've reached the size they should be. The cells would divide when they were still very short," said Levin. "It was almost as if they were growing in really great media but they didn't know it."
Knowing when to divide