Biomedical Engineering Reference
In-Depth Information
nesin and dynein do not readily dissociate from these organelles, once attached
[95]. Do these two oppositely directed motors work against each other in a
tug-of-war, or do they somehow coordinate their movements? Several experi-
ments indicate that their movements may be coordinated. Movement of lipid
droplets connected to both kinesin and dynein is inhibited in both directions
by mutations that slow dynein's movement only, indicating that dynein as-
sists kinesin's processivity [96]. The mechanism of cooperation between the
two motors may involve dynactin, which has been shown to have a single
binding site for both kinesin II and dynein in
Xenopus
melanophores [97].
Surprisingly, even at the level of single motor steps, kinesin and dynein
motors on single organelles appear to cooperate. Kural and colleagues tracked
the movement of peroxisomes
in vivo
with a precision of a few nanometers.
They observed organelles with both kinesin and dynein attached, which made
several discrete 8 nm steps in one direction, then reversed, and took sev-
eral more steps. One cargo could reverse and take several unidirectional, 8
nm steps several times [98]. Purely random connections between motor and
cargo would not predict this behavior because opposing motions of the two
motors would lead to the observation of intermediate step sizes. This result
demonstrates that not only do kinesin and dynein appear to cooperate, but
their coordination is extremely rapid, such that an organelle can switch direc-
tions in milliseconds without any apparent pause in movement or tug-of-war
between the two motors.
The mechanism of such a coordinator would require energy to switch in-
stantly between kinesin and dynein motor movement, which perhaps could
be harnessed “parasitically” from the ATPase activity of the two motors it
controls. Alternatively, the coordinator could have ATPase or GTPase activ-
ity of its own, which would enable several mechanisms of external control.
Regardless of how this part of the story turns out, it will be interesting to
see how the vast array of cargo-binding and regulatory mechanisms can yield
fairly simple and sensitive cellular responses to particular cues.
