2009-ASCB-Press-Book - page 6

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
49th Annual Meeting
San Diego, CA
December 5–9, 2009
One-way neurons no more
10:00 am, U.S. Pacific Time
Sunday, December 6, 2009
Michelle C. Stone
Pennsylvania State University
114 Life Sciences
University Park, PA 16802
(814) 867-1396
Melissa M. Rolls
Pennsylvania State University
University Park, PA 16802
(814) 867-1395
Authors present
Sunday, December 6, 2009
10:15–10:35 am
Minisymposium 3: Cell Polarity
Program 19
Room 28A–E
Reversal of Neuronal Polarity
after Axon Removal: Converting
a Dendrite into a Regenerating
Axon by Rebuilding the Micro-
tubule Cytoskeleton
M.C. Stone, M.M. Nguyen,
J. Tao, M.M. Rolls
Biochemistry and Molecular
Biology, The Pennsylvania
State University, University
Park, PA
After an axon injury, a fruit fly
neuron can regenerate by reversing
the polarity of a dendrite so that it
can be transformed into an axon
n injured neuron, severed from its
long, narrow, signal-sending axon,
can reprogram one of its signal-
receiving dendrites as a first step toward
regeneration. These findings in fruit flies
by researchers at Pennsylvania State
University reveal a remarkable ability of
normally stable neurons to rebuild them-
selves in the face of injury.
Michelle Stone, Melissa Rolls, and
colleagues at Penn State report that
dendrites, the bushy, signal-receiving
extensions in the neuron, reshuffle their
cytoskeleton after axonal injury until
one dendrite switches its polarity and
grows into a permanent replacement for
the missing axon. Axon regeneration is
crucial for recovery after trauma to the
nervous system. Insights into how sev-
ered axons in
Drosophila melanogaster
about regeneration could offer new clues
for treating traumatic nerve damage or
neurodegenerative disease in people.
Once formed, neurons are normally
relatively staid. It’s in the nature of their
job to make dendrites plus a single axon
and then to maintain them throughout
life. For this long-term organization, neu-
rons need a stable cytoskeleton, explains
Stone. The basic units of the cytoskeleton
To perform in vivo axon severing, whole Drosophila larvae are mounted
on slides. The larvae express fluorescent-tagged markers in two to three
neurons per hemi-segment (cell bodies, dendrites, and axons indicated
with arrows). An aimed, pulsed UV laser cuts through one of the axons.
The animals can then be removed to recover in their normal food, and
mounted for imaging again at later time points.
are microtubules, polymerized proteins
that stack up into a strong, stable, and
highly polarized cellular backbone that
also acts as an internal trackway for long-
range intracellular transport. The polarity
of the microtubules in axons and dendrites
is different, in keeping with the different
roles of these cellular structures.
That’s why it was so surprising, says
Stone, to see how powerfully dendritic
microtubules reacted when researchers
used a laser to cut off the entire axon of a
neuron. The supposedly stable
microtubules burst into action, essentially
deconstructing and rebuilding the entire
dendritic microtubule cytoskeleton. Grow-
ing microtubules dramatically increased
in number and their polarity became fluid.
This dynamic microtubule response, the
researchers report, was specific to axon,
not dendrite, injury.
It took two to three days after the
injury for one dendrite to take on its new
axonal microtubule polarity (i.e., with the
plus end out) and finally begin forming
an axon. Microtubule dynamics settled
down in the remaining dendrites, assum-
ing the normal minus-end-out polarity at
this point, so that the overall layout of the
cell resembled that before injury—a single
axon and several dendrites with opposite
microtubule orientation.
Stone and colleagues believe that
exploring microtubule control is critical
to understanding how axons regener-
ate from dendrites. By
manipulating levels of
intracellular proteins, the
researchers discovered
that they could speed
up the dendrite-to-axon
transformation by slow-
ing down microtubule
dynamics. This antago-
nism could be important
to allow the neuron to
repolarize its microtubules
correctly before growing
the new axon, they sug-
gest. Finding the exact
mechanisms that control
dendrite regeneration is
the work ahead.
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