Biology Reference
In-Depth Information
18.1 Introduction
Neurons are arguably the cell type in nature with the greatest dependence upon
sophisticated arrays of highly organized microtubules for their form and function.
A typical vertebrate neuron extends a single axon and multiple dendrites, both of
which are rich in microtubules. The microtubule arrays within these processes are
essential for providing architectural support, for enabling axons and dendrites to
take on different shapes and branching patterns, and for supporting bidirectional
organelle transport (Baas and Buster
2004
). Many of the most fundamental dif-
ferences between axons and dendrites directly or indirectly result from distinct
patterns of microtubule orientation in each type of process. In the axon, nearly all
of the microtubules are oriented with their plus ends distal to the cell body,
whereas in the dendrite, the microtubules have a mixed pattern of orientation (Baas
and Lin
2011
). In most textbooks, microtubules are said to be organized mainly by
their attachment to microtubule-organizing centers such as the centrosome
(Alberts et al.
2007
), but amazingly, the highly organized microtubules in axons
and dendrites are not attached to the centrosome or any recognizable organizing
structure (Baas and Yu
1996
). Instead, the microtubules are free at both ends, and
take on various lengths within the axon and dendrites. The shortest microtubules
are highly mobile, moving rapidly within the axon (Wang and Brown
2002
) and
perhaps the dendrite as well (Sharp et al.
1995
). One of the questions that has
driven our laboratory for many years is how microtubules become organized in the
axon and dendrites if not via attachment to an organizing center. Another question
is whether the centrosome (located in the cell body of the neuron) has any
importance for generating or organizing the neuronal microtubule arrays, or
alternatively, whether it is a vestigial structure with no function.
Over a decade ago, we embarked on a series of studies the results of which led
us to propose that the neuronal centrosome acts as a ''generator'' of microtubules
for the axon and dendrites (Ahmad and Baas
1995
; Ahmad et al.
1994
,
1998
,
1999
;
Baas
1996
; Yu et al.
1993
). The premise was that the neuronal centrosome is
highly active, especially during development, nucleating and releasing microtu-
bules into the cell body. The released microtubules are then actively transported
into the axon and dendrites by molecular motor proteins. The relevant motors
transport the microtubules specifically with their plus or minus end leading, and
thereby establish the distinct patterns of microtubule polarity orientation in each
type of process (Baas and Ahmad
1993
; Sharp et al.
1995
,
1997
; Yu et al.
1997
). In
this view, the centrosome does not contribute to the polarity orientation of
microtubules in either type of process, except perhaps to create an initial bias of
plus ends outward in the cell body as the microtubules transit away from the
centrosome (Ahmad and Baas
1995
). One of the main roles that we envisioned for
the centrosome was to nucleate microtubules in a regulated fashion with the
appropriate lattice structure, as de novo nucleation of microtubules would pre-
sumably result in a variety of different protofilament numbers comprising the
lattice (Baas and Joshi
1992
; Yu et al.
1993
). Another role for the centrosome, as a
