Biology Reference
In-Depth Information
Start
Correct endpoint
Road closed
One-way street
Driving ban
Faulty signals
No parking
Reduced traffic flow
Figure 5.1. Specific defects in axonal transport. Movement of axonal transport cargoes anterogra-
dely (blue) and retrogradely (red) over a fixed period of time. Top right: normal
endpoint. Below: six ways in which axonal transport can fail to deliver all cargoes to
their correct locations (see text for corresponding examples).
nerve constituents were found to travel retrogradely as well as anterogradely
(Lubinska, 1964). Then, slow anterograde transport was discovered and subdi-
vided (Lasek, 1968). Today, we know a huge array of anterograde motor proteins
of the kinesin superfamily carrying different cargoes at different speeds
(Hirokawa and Noda, 2008), together with adapter proteins whose roles in
regulating attachment of cargo to motor proteins are just beginning to emerge
(Horiuchi
, 2005; Wang and Schwarz, 2009). The range of specific faults
that can affect axonal transport is correspondingly wide, resulting in unidirec-
tional impairment, partial impairment, or failure to deliver specific cargoes or
groups of cargoes (Fig. 5.1).
et al.
C. One-way street! Unidirectional transport impairment
The microtubule-associated protein tau has emerged as an important modulator
of axonal transport, but it has differential effects on anterograde and retrograde
transport. Tau overexpression slows anterograde transport of mitochondria more
than retrograde in cell lines (Stamer
, 2002), probably reflecting its ability to
dissociate the anterograde motor kinesin from microtubules. In contrast, when
the retrograde motor dynein encounters tau, it hesitates but does not dissociate
(Dixit
et al.
, 2008). In amyotrophic lateral sclerosis studies, primary motoneuro-
nal cultures from the SOD1
G93A
transgenic mouse model show reduced antero-
grade transport of mitochondria and enhanced retrograde transport, which may
deplete axons of mitochondria (De Vos
et al.
et al.
, 2007). One intriguing possibility is
