2013 Annual Meeting Abstracts - page 825

be directly attached to it. In neurons expressing td-EOS-tubulin, regions of the MT array converted from
green to red fluorescence displayed movements both during bouts of migration as well as during pausing.
The MT movements generally were in the forward direction in the leading process when the neuron
migrated but were more often in the retrograde direction during pauses. Sometimes, individual MTs
displayed a complexity of movements, splaying apart from one another, especially in the more distal
regions of the leading process. Based on these observations, we propose that migrating neurons contain
a population of centrosome-attached MT, able to function as previously discussed in the neuronal
migration field, but also a population of centrosome-detached MTs that undergo unprecedented sliding
movements with potentially important roles to play in neuronal migration.
Fidgetin restrains axonal growth during neuronal maturation by a microtubule-
based mechanism and provides a means for therapeutically enhancing
regeneration of injured adult axons
L. Leo
, T. O. Austin
, W. Yu
, D. R. Marenda
, D. J. Sharp
, P. W. Baas
Neurobiology and Anatomy,
Drexel University College of Medicine, Philadelphia, PA,
Biology, Drexel University, Philadelphia, PA,
Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY
During development, axons grow rapidly and then stop growing when they reach appropriate target
tissues. In some cases, axons overgrow and need to be pruned back. In the adult nervous system,
injured axons face the dilemma of having to resume growth after decades of non-growth, typically in an
environment rife with inhibitory cues. A greater proportion of the microtubule mass in developing axons is
highly dynamic compared to that of adult axons, and this presumably is related to the greater intrinsic
capacity of axons to grow during development. Here we studied fidgetin, an enzyme shown to have
microtubule-severing properties in recent in vitro studies. Depletion of fidgetin from cultured embryonic
neurons causes their axons to grow notably faster, while its depletion from the neurons of Drosophila
causes axons to overgrow their normal targets. Using a novel nanoparticle-encapsulated approach for
delivery of the siRNA, we found that when fidgetin is depleted, the axons of adult neurons in culture also
display a boost in axonal growth rate, as well as an enhanced capacity to grow on inhibitory substrates.
Interestingly, microtubule and tubulin levels are higher after fidgetin depletion but the levels of post-
translationally acetylated tubulin are lower. As the levels of tubulin acetylation are known to increase as
neurons mature, the lowering of the ratio of acetylated to total tubulin levels presumably reflects a
restoration of the microtubule array to a more juvenile status. This conclusion is supported by drug
studies indicating that neurons depleted of fidgetin possess a greater proportion of dynamic versus stable
microtubule polymer. Interestingly, fidgetin levels are roughly twice as high in developing neurons
compared to adult neurons, suggesting a greater role for fidgetin in sculpting the microtubule array when
it is more dynamic. We posit that fidgetin plays an important role during neuronal development in paring
down the more dynamic microtubule polymer to regulate axonal growth and pruning, and ultimately to
establish a more stable microtubule array consistent with the cessation of axonal growth. Our novel
nanoparticle approach for depleting fidgetin from adult neurons provides an exciting new avenue for
treating patients with nerve injuries.
Microtubule-associated protein 1B (MAP1B) regulates synaptic functions in
mature neurons
F. Bodaleo
, C. Montenegro-Venegas
, F. Court
, S. Hartel
, C. Gonzalez-Billault
Universidad de Chile,
Santiago, Chile,
Universidad Catolica de Chile, Santiago, Chile
Microtubule-associated protein 1B (MAP1B) is predominantly expressed during early stages of the
development of the nervous system, where it plays a crucial role in axonal growth, neuronal migration and
axonal guide. However its expression is down-regulated in later stages except in brain areas with high
plasticity like the cortex and hippocampus. According with this MAP1B is present in mature hippocampal
neurons cultured 21 days in vitro (DIV) specifically at dendritic spines. Neurons derived from MAP1B-
deficent mice present a reduction in the density of total dendritic spines. Three dimentional
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