LGN blocks the ability of NuMA to bind and stabilize microtubules

A mechanism for mitotic spindle assembly regulation

Quansheng Du, Laura Taylor, Duane A. Compton, Ian G. Macara

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1928-1933
Number of pages6
JournalCurrent Biology
Volume12
Issue number22
DOIs
StatePublished - Nov 19 2002
Externally publishedYes

Fingerprint

mitotic spindle apparatus
Spindle Apparatus
Microtubules
microtubules
Cells
Stabilization
Asymmetric Cell Division
Spindle Poles
Nuclear Localization Signals
nuclear localization signals
nuclear proteins
pins
Nuclear Proteins
Mitosis
Anura
mitosis
Embryonic Development
Ovum
cell division
frogs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

LGN blocks the ability of NuMA to bind and stabilize microtubules : A mechanism for mitotic spindle assembly regulation. / Du, Quansheng; Taylor, Laura; Compton, Duane A.; Macara, Ian G.

In: Current Biology, Vol. 12, No. 22, 19.11.2002, p. 1928-1933.

Research output: Contribution to journalArticle

Du, Quansheng ; Taylor, Laura ; Compton, Duane A. ; Macara, Ian G. / LGN blocks the ability of NuMA to bind and stabilize microtubules : A mechanism for mitotic spindle assembly regulation. In: Current Biology. 2002 ; Vol. 12, No. 22. pp. 1928-1933.
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