Biology Reference
In-Depth Information
microtubules in living neurons moving from the centrosome into the axon. The
issue arises as to whether the centrosome is actually needed under normal
circumstances, or whether our pharmacologic regimes stress the system to a point
where an otherwise unnecessary centrosome becomes necessary. In support of our
interpretation, the active release of microtubules from the centrosome has been
directly visualized in cellular extracts (Belmont et al.
1990
) as well as living
epithelial cells in a regime that involved no drug treatments (Keating et al.
1997
).
Moreover, in the case of the neuron, we have also shown that inhibition of katanin,
a microtubule-severing protein, prohibits microtubule release from the centro-
some, which in turn precludes the appearance of free microtubules in our phar-
macologic regime (Ahmad et al.
1999
).
18.5 Newer Data on Microtubules and the Neuronal
Centrosome
Over a decade after our spate of papers on the neuronal centrosome, the laboratory
of Frank Bradke has recently challenged the idea of the neuronal centrosome
acting as a generator of microtubules for axons and dendrites (Stiess and Bradke
2010
; Stiess et al.
2010
). They favor the alternative view that the centrosome is
dismantled during neuronal development such that its microtubule-nucleating
duties are spread to new locations in the neuron, such as within the axon and
dendrite themselves. This scenario would be similar to what has been shown for
muscle cells, in which gamma-tubulin and its associated microtubule-nucleating
properties are redistributed to the nuclear membrane and other sites within the
cytoplasm (Bugnard et al.
2005
). In fact, consistent with our original speculation
for how a non-uniform microtubule polarity pattern might arise in dendrites (Baas
et al. Baas et al.
1988
,
1989
), at least one pericentriolar protein has been shown to
be present in dendrites but not axons (Ferreira et al.
1993
). It is also provocative
with regard to the centrosome dismantling hypothesis for neurons that Leask and
colleagues reported a steady diminution in gamma-tubulin from the centrosome as
dorsal root ganglion neurons mature, which would be consistent with a gradual
redistribution of their pericentriolar proteins (Leask et al.
1997
). Bradke's group
found a similar diminution of gamma-tubulin levels as well as another key protein
component of the c-TuRCs, consistent with the idea that the capacity of the
neuronal centrosome to act as a generator of microtubules wanes as the neuron
matures. In addition, they found with hippocampal neurons that the nocodazole
recovery regime resulted in a burst of microtubules from the centrosome early in
development (Dotti and Banker
1991
), but this was not the case later in devel-
opment. In cultures that were several days old, neurons bearing dendrites showed
no specific
recovery of
microtubules from
the centrosome after
nocodazole
treatment
and
removal.
Instead,
the
microtubules
reassembled
from
sites
throughout the cell body (Stiess et al.
2010
).
