Microtubule motors in mitosis

Abstract

The mitotic spindle uses microtubule-based motor proteins to assemble itself and to segregate sister chromatids. It is becoming clear that motors invoke several distinct mechanisms to generate the forces that drive mitosis. Moreover, in carrying out its function, the spindle appears to pass through a series of transient steady-state structures, each established by a delicate balance of forces generated by multiple complementary and antagonistic motors. Transitions from one steady state to the next can occur when a change in the activity of a subset of mitotic motors tips the balance.

LIS1—no more no less

“…25 Dynein, dynactin and LIS1 co-immunoprecipitate and colocalize in tissue culture and in the brain. 26,27 Microtubule-based motor proteins are essential components of the mitotic spindle and are required for segregation of sister chromatids (recently reviewed by Sharp et al 28 ). Indeed, overexpression of LIS1 in cultured mammalian cells interfered with mitotic progression and led to spindle misorientation.…”

Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl-l-cysteine in tumor derived cell lines

“…The Eg5 tetramer has the ability to crosslink antiparallel microtubules emanating from the two centrosomes at G2/M. Through its plus-end directed microtubule-based motor activity Eg5 is capable of generating outward forces which contribute to the separation of the two centrosomes, a process which is essential for the successful establishment of a bipolar spindle during mitosis [3,4].…”

Kinesin motors as molecular machines

“…2). (18)(19)(20) The motors can bind to and crosslink spindle fibers and use energy from ATP hydrolysis to move directionally along microtubules, performing essential roles in spindle assembly and maintenance, centrosome duplication, and attachment of centrosomes to poles. Several of the kinesin motors are associated with chromosomes and may play a role in mediating chromosome attachment to the spindle (21) or congression to the metaphase plate.…”