TY - JOUR
T1 - LGN blocks the ability of NuMA to bind and stabilize microtubules
T2 - A mechanism for mitotic spindle assembly regulation
AU - Du, Quansheng
AU - Taylor, Laura
AU - Compton, Duane A.
AU - Macara, Ian G.
N1 - Funding Information:
We thank Dr. P. Todd Stukenberg for providing Xenopus egg extracts and the members of the Macara lab for useful discussions. This work was supported by grant CA40042 to I.G.M. and grant GM51542 to D.A.C., from the National Institutes of Health, Department of Health and Human Services.
PY - 2002/11/19
Y1 - 2002/11/19
N2 - LGN is closely related to a Drosophila protein, Partner of inscuteable (Pins), which is required for polarity establishment and asymmetric cell divisions during embryonic development [1-3]. In mammalian cells, LGN binds with high affinity to the C-terminal tail of NuMA, a large nuclear protein that is required for spindle organization, and accumulates at the spindle poles during mitosis [4-9]. LGN also regulates spindle organization, possibly through inhibition of NuMA function [10], but the mechanism of this effect has not yet been understood. Using mammalian cells, frog egg extracts, and in vitro assays, we now show that a small domain within the C terminus of NuMA stabilizes microtubules (MTs), and that LGN blocks stabilization. The nuclear localization signal adjacent to this domain is not involved in stabilization. NuMA can interact directly with MTs, and the MT binding domain on NuMA overlaps by ten amino acid residues with the LGN binding domain. We therefore propose that a simple steric exclusion model can explain the inhibitory effect of LGN on NuMA-dependent mitotic spindle organization.
AB - LGN is closely related to a Drosophila protein, Partner of inscuteable (Pins), which is required for polarity establishment and asymmetric cell divisions during embryonic development [1-3]. In mammalian cells, LGN binds with high affinity to the C-terminal tail of NuMA, a large nuclear protein that is required for spindle organization, and accumulates at the spindle poles during mitosis [4-9]. LGN also regulates spindle organization, possibly through inhibition of NuMA function [10], but the mechanism of this effect has not yet been understood. Using mammalian cells, frog egg extracts, and in vitro assays, we now show that a small domain within the C terminus of NuMA stabilizes microtubules (MTs), and that LGN blocks stabilization. The nuclear localization signal adjacent to this domain is not involved in stabilization. NuMA can interact directly with MTs, and the MT binding domain on NuMA overlaps by ten amino acid residues with the LGN binding domain. We therefore propose that a simple steric exclusion model can explain the inhibitory effect of LGN on NuMA-dependent mitotic spindle organization.
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U2 - 10.1016/S0960-9822(02)01298-8
DO - 10.1016/S0960-9822(02)01298-8
M3 - Article
C2 - 12445386
AN - SCOPUS:0037137429
SN - 0960-9822
VL - 12
SP - 1928
EP - 1933
JO - Current Biology
JF - Current Biology
IS - 22
ER -