Figure 2.

NuMA functions at spindle poles to bundle and tether microtubules. (a) Schematic of the mitotic spindle, representing kinetochore (light green) and non-kinetochore (dark green) microtubules. The spindle pole (square box) is enlarged in (b). NuMA (blue squiggle) cross-links kinetochore and non-kinetochore microtubules at the spindle pole. NuMA containing complexes involved in microtubule linkage at the spindle poles form a structure equivalent to a “spindle pole matrix” (large hatched oval). (c) Proteins interacting with NuMA at spindle poles (enlarged square box from (b)). During nuclear breakdown, NuMA is phosphorylated (yellow) at four putative p34^cdc2 sites (threonine 2000, 2040, 2091, serine 2072) [23, 25]. Mitotically phosphorylated NuMA associates with dynein (pink), which carries it in a minus-end directed fashion (pink arrow) and deposits it at spindle poles where it functions in spindle maintenance via microtubule tethering [20]. A NuMA dimer (dark blue, top) cross-links microtubules through interactions mediated by its C-terminal microtubule binding domain and the associated dynein (pink) [6, 7]. Rae1, a messenger RNA transport protein (blue triangle), may also mediate binding of the NuMA N-termini to microtubules [38], thus transiently generating a higher level of parallel microtubule bundling (bottom microtubules). (d) Emi1 (gray), an inhibitor of Cdc20 dependent activation of the anaphase promoting complex (APC), has been proposed to exist in a complex with dynein and NuMA prior to anaphase [28], as a means of sequestering APCCdc20 (yellow) away from the general cytoplasm. (e) A possible mechanism for NuMA dissociation from microtubules. LGN (red), by competing with microtubules for NuMA binding, acts as a negative regulator of NuMA bundling [7] and may be responsible for the relocalization of a NuMA subset from the spindle pole to the cell cortex.