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Florida State researcher uncovers protein's role in cell division
Date:6/15/2010

DK5RAP2 was at least partly responsible. His team tested the protein's role using a mutant mouse in which the protein was "knocked out" and not functioning. These researchers looked for any effects on engagement and "cohesion," in which centriole pairs are tethered by fibers.

They noted in the mutant mouse that engagement and cohesion did not occur in their typical orderly fashion and that centrioles were more numerous and often single rather than paired. The amplified centrioles assembled multipolar spindles, a potential hazard for chromosomal stability. The researchers concluded that CDK5RAP2 is required to maintain centriole engagement and cohesion, thereby restricting centriole replication.

They are looking at how this discovery might apply to the human brain.

"The two mouse mutants we made mimic the two known mutations in humans in CDK5RAP2 which has another name, MCPH3, in humans," Megraw said. "The disease associated with that is a small brain.

"Our next step is to look at the brains of the mice and try to determine what's wrong. We think it's the stem cells that the progenitors that give rise to all the neurons in the brain are dying early or changing from a progenitor into a neuron too early."

Another gene called myomegalin might be functionally redundant to CDK5RAP2, Megraw said, adding, "Our goal is to knock that out, too."

The research his lab has done might also be applicable to cancer drugs for humans, he said. Centrosomes organize microtubules, which are structures in the cell that many important anti-cancer drugs target.

"The amplified centrioles and multipolar spindles suggest that the mutant mice may be more susceptible to developing cancers," Megraw said. "We are in a position to test this with our new mouse models."


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Contact: Timothy Megraw
timothy.megraw@med.fsu.edu
850-945-9271
Florida State University
Source:Eurekalert  

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