How an enzyme tells stem cells which way to divide

May 14, 2009
aPKC is shown in green at the top half of a fruit fly neuroblast. Miranda, in blue, has been driven away to the opposite side. Upon division, the top half will remain a stem cell, while the bottom will become a differentiated cell. Credit: Courtesy of Kenneth Prehoda

Driving Miranda, a protein in fruit flies crucial to switch a stem cell's fate, is not as complex as biologists thought, according to University of Oregon biochemists. They've found that one enzyme (aPKC) stands alone and acts as a traffic cop that directs which roads daughter cells will take.

"Wherever aPKC is at on a cell's cortex or membrane, Miranda isn't," says Kenneth E. Prehoda, a professor in the chemistry department and member of the UO's Institute of Molecular Biology. When a stem cell duplicates into , the side, or cortical domain, containing aPKC (atypical protein kinase C) continues as a stem cell, while the other domain with Miranda becomes a differentiated cell such as a neuron that forms the .

Prehoda and co-author Scott X. Atwood, who studied in Prehoda's lab and recently earned his doctorate, describe how the mechanism works in the May 12 issue of the journal Current Biology.

Instead of a complex cascade of protein deactivation steps that many biologists have theorized, Prehoda said, aPKC strips phosphate off an energy-transfer known as ATP and then attaches it to Miranda. This process forces Miranda away from aPKC and helps determine the fates of subsequent daughter cells.

"This process is pretty simple," he said, when viewed from a biochemical perspective. "What happens is that Miranda gets phosphorylated by aPKC, turning it into an inactivated substrate and pushing it into another location in the cell."

Much of the paper in is devoted to why the more complex scenarios are not accurate. "There have been a lot of ideas on how this works, and most seemed to be really complicated and difficult to explain. We have found it's a much simpler mechanism," Prehoda said, adding that the mechanism likely is similar in many other types of cells, not just .

"It's a basic-research question. How does this polarity occur? In order to develop stem cell-specific therapeutics based on a rational methodology you have to understand the mechanism," he said.

If Miranda is improperly isolated into other regions by aPKC, the stem cell divides symmetrically, with both daughter cells adopting the same fate, In turn, Prehoda said, these cells can become tumorous as they continue to rapidly divide without proper .

Source: University of Oregon (news : web)

Explore further: Japan lab cannot repeat ground-breaking cell finding: reports

add to favorites email to friend print save as pdf

Related Stories

Building brains: Mammalian-like neurogenesis in fruit flies

Feb 19, 2008

A new way of generating brain cells has been uncovered in Drosophila. The findings, published this week in the online open access journal Neural Development, reveal that this novel mode of neurogenesis is very similar to tha ...

New evidence that stem cells contain immortal DNA

Jun 27, 2006

EuroStemCell scientists at the Pasteur Institute in Paris have demonstrated one of the body’s most sophisticated ways of regulating the genetic material of stem cells. Their findings, published in Nature Cell Biology, show f ...

Recommended for you

'Hairclip' protein mechanism explained

11 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

Discovery in the fight against antibiotic-resistant bacteria

13 hours ago

For four years, researchers at Universite catholique de Louvain have been trying to find out how bacteria can withstand antibiotics, so as to be able to attack them more effectively. These researchers now understand how one ...

Stem cells born out of indecision

13 hours ago

Scientists at the University of Copenhagen have gained new insight into embryonic stem cells and how blocking their ability to make choices explains why they stay as stem cells in culture. The results have just been published ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.