such as "Introduction", "Conclusion"..etc
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 daughter cells, 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 central nervous system.
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 nucleotide 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 Current Biology 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 stem cells.
"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 polarization.
The National Institutes of Health supported the research through a
Developmental Biology Training Grant to Atwood and a research grant to
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