Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 115

A B

Burbank et al. Loughlin et al.

Flux rate Flux rate

Nucleation zones MT depolymerization

Clustering motor (dynein) Transport motor (dynein)

Sliding motor (kinesin-5)

Minus-end crosslinking

Figure 3.9 Computational simulations of spindle architecture establish MT lifetime as a
critical factor for setting spindle size and two complementary mechanisms of pole for-
mation. (A) The model developed by Burbank et al. utilized an outward sliding force on
antiparallel MTs, similar to the known functions of the kinesin-5 proteins, and a cluster-
ing force, similar to dynein, to generate a system where spindle length was regulated
and poles formed at the balance point of outward sliding and clustering forces. Nucle-
ation of MTs in this simulation was near the center of the spindle. (B) The model by
Loughlin et al. utilized an outward sliding force on antiparallel MTs, a dynein-like trans-
port molecule with minimal clustering capability, and a MT-depolymerizing activity sim-
ilar to kinesin-13s. Again, spindle length could be regulated and poles formed. However,
pole formation occurred at the point where outward sliding and depolymerization were
balanced. Nucleation in this model was both in the center of the spindle but also dis-
tributed throughout the body in a MT-branching type nucleation.

occurred near the center of the spindle; however, the model by Loughlin
et al. also implemented nucleation throughout the spindle similar to that
expected for branching MT nucleation. With common approaches to sim-
ulating minimal spindle systems, both models led to a similar conclusion
about spindle architecture. Qualitatively, both models (1) produced a high
concentration of minus-ends defining the spindle poles, with some still dis-
tributed throughout the spindle, (2) did not require a complex restoring
force beyond the few motors (or other enzymes) in the simulation, and
(3) showed that the lifetime of the MT within the spindle primarily con-
trolled spindle length.
The major difference that emerges from these two models, and one that
predicts significant architectural differences in the spindle, is the difference in
the transport rate of MTs. In the model by Burbank et al., MTs slow as they
near the pole due to force generated by the clustering motor that opposes the