Intramolecular interaction in LGN, an adaptor protein that regulates mitotic spindle orientation

Hiroki Takayanagi, Junya Hayase, Sachiko Kamakura, Kei Miyano, Kanako Chishiki, Satoru Yuzawa, Hideki Sumimoto

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

Proper mitotic spindle orientation requires that astral microtubules are connected to the cell cortex by the microtubulebinding protein NuMA, which is recruited from the cytoplasm. Cortical recruitment of NuMA is at least partially mediated via direct binding to the adaptor protein LGN. LGN normally adopts a closed conformation via an intramolecular interaction between its N-terminal NuMA-binding domain and its C-terminal region that contains four GoLoco (GL) motifs, each capable of binding to the membrane-anchored Gαi subunit of heterotrimeric G protein. Here we show that the intramolecular association with the N-terminal domain inLGNinvolves GL3, GL4, and a region between GL2 and GL3, whereas GL1 and GL2 do not play a major role. This conformation renders GL1 but not the other GL motifs in a state easily accessible to Gαi. To interact with full-length LGN in a closed state, NuMA requires the presence of Gαi; both NuMA and Gαi are essential for cortical recruitment of LGN in mitotic cells. In contrast, mInsc, a protein that competes withNuMAfor binding toLGNand regulates mitotic spindle orientation in asymmetric cell division, efficiently binds to full-length LGN without Gαi and induces its conformational change, enhancing its association with Gαi. In nonpolarized symmetrically dividing HeLa cells, disruption of the LGN-NuMA interaction by ectopic expression of mInsc results in a loss of cortical localization of NuMA during metaphase and anaphase and promotes mitotic spindle misorientation and a delayed anaphase progression. These findings highlight a specific role for LGN-mediated cell cortex recruitment of NuMA.

本文言語英語
ページ(範囲)19655-19666
ページ数12
ジャーナルJournal of Biological Chemistry
294
51
DOI
出版ステータス出版済み - 12 20 2019
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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