Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins

Quansheng Du, Ian G. Macara

Research output: Contribution to journalArticle

273 Scopus citations

Abstract

During asymmetric cell divisions, mitotic spindles align along the axis of polarization. In invertebrates, spindle positioning requires Pins or related proteins and a G protein α subunit. A mammalian Pins, called LGN, binds Gαi and also interacts through an N-terminal domain with the microtubule binding protein NuMA. During mitosis, LGN recruits NuMA to the cell cortex, while cortical association of LGN itself requires the C-terminal Gα binding domain. Using a FRET biosensor, we find that LGN behaves as a conformational switch: in its closed state, the N and C termini interact, but NuMA or Gαi can disrupt this association, allowing LGN to interact simultaneously with both proteins, resulting in their cortical localization. Overexpression of Gαi or YFP-LGN causes a pronounced oscillation of metaphase spindles, and NuMA binding to LGN is required for these spindle movements. We propose that a related switch mechanism might operate in asymmetric cell divisions in the fly and nematode.

Original languageEnglish (US)
Pages (from-to)503-516
Number of pages14
JournalCell
Volume119
Issue number4
DOIs
StatePublished - Nov 12 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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