Notably, MTs assembled from pure tubulin do not treadmill at steady-state as initially thought by Margolis and Wilson ( Margolis and Wilson, 1978) instead their plus- and minus-ends exhibit dynamic instability ( Grego et al., 2001). During anaphase, features of this system could be modulated to precipitate anaphase events for example, the cessation of kMT plus-end assembly would lead to the segregation of disjoined sister chromatids to their respective poles. During metaphase, the coordinated poleward sliding of crosslinked, treadmilling MTs would create an isometric tension in the spindle. If kMTs were linked to the translocating ipMTs by crossbridges, then chromosomes attached to the kMTs would experience a poleward force. Where the two half-spindles overlap at the spindle equator, the ATP-dependent sliding apart of the anti-parallel ipMTs would result in poleward translocation of MTs. proposed that the parallel MTs in each half-spindle treadmill while their plus-ends (at kinetochores and in the spindle equator) assemble by tubulin subunit addition and their minus-ends (at spindle poles) simultaneously disassemble by tubulin loss ( Margolis et al., 1978). The subsequent discovery of MT treadmilling ( Margolis and Wilson, 1978) led to a theoretical model of spindle function based on the poleward flow of the MT array. Importantly, the major source of MT assembly dynamics in the spindle is plus-end dynamic instability, which is not shown here for simplicity. Likewise, opposing blue arrows indicate the metaphase plateward direction of force exerted by flux on each spindle pole. Orange arrows above the spindle indicate the poleward direction of force exerted by flux on each sister kinetochore. Astral MTs (green lines), whose minus-ends are embedded in the centrosomes, do not flux. kMT plus-end assembly stops at the transition to anaphase (although there are exceptions to this rule) ( Chen and Zhang, 2004 LaFountain et al., 2004) (see text). Arrows within the red and blue lines indicate the direction of continuous ATP-dependent polymer movement. Tubulin subunits are incorporated into polymer at MT plus-ends and removed at their minus-ends focused at the spindle poles. Flux occurs on both kMTs (red lines) and non-kMTs (blue lines) in the spindle. Poleward MT flux in a metaphase-stage mitotic spindle. Here, we discuss the impact of an important force-generating engine in the spindle – poleward MT flux – whose function, until recently, was mostly speculation. Successful chromosome segregation requires proper assembly and function of the spindle MT array and, although numerous studies have identified MT-dependent forces underlying chromosome movement and spindle assembly ( Mitchison and Salmon, 2001), we possess an incomplete understanding of the force-generating components. Finally, astral MTs project from poles towards the cell cortex ( Fig. Interpolar MTs (ipMTs) extend towards the spindle equator and may interact with MTs from the opposite pole. Kinetochore MTs (kMTs) dock with kinetochores, which are multiprotein complexes assembled onto centromeric DNA ( Maiato et al., 2004), and bundle together to form kinetochore fibers (K-fibers). Within the spindle, MTs are distinguished further by their positions, and these differences are relevant to their respective functions. Different pathways can be used by cells to assemble the array of filamentous MTs to form the characteristic bipolar spindle ( Budde and Heald, 2003 Wadsworth and Khodjakov, 2004), in which MT plus-ends are directed towards the spindle center and MT minus-ends are focused into poles at either end of the spindle. The eukaryotic spindle is a fusiform-shaped, microtubule (MT)-based machine that primarily serves a single purpose: the proper separation of chromosomes in meiotic and mitotic cells ( Wittmann et al., 2001).
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