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Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics.

EMBO J.2018 Jul 02;37(13). Epub 2018 Jun 01
Lene Malerød 1 , Roland Le Borgne 2 , Anette Lie-Jensen 1 , Åsmund Husabø Eikenes 3 , Andreas Brech 1 , Knut Liestøl 4 , Harald Stenmark 1 , Kaisa Haglund 1
Lene Malerød 1 , Roland Le Borgne 2 , Anette Lie-Jensen 1 , Åsmund Husabø Eikenes 3 , Andreas Brech 1 , Knut Liestøl 4 , Harald Stenmark 1 , Kaisa Haglund 1
+ et al

[No authors listed]

Author information
  • 1 Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • 2 Equipe labélisée Ligue Contre Le Cancer, Rennes, France.
  • 3 Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • 4 Department of Informatics, University of Oslo, Oslo, Norway.

摘要


The orientation of the mitotic spindle (MS) is tightly regulated, but the molecular mechanisms are incompletely understood. Here we report a novel role for the multifunctional adaptor protein ALG-2-interacting protein X (ALIX) in regulating MS orientation in addition to its well-established role in cytokinesis. We show that ALIX is recruited to the pericentriolar material (PCM) of the centrosomes and promotes correct orientation of the MS in asymmetrically dividing Drosophila stem cells and epithelial cells, and symmetrically dividing Drosophila and human epithelial cells. ALIX-deprived cells display defective formation of astral microtubules (MTs), which results in abnormal MS orientation. Specifically, ALIX is recruited to the PCM via Drosophila Spindle defective 2 (DSpd-2)/Cep192, where ALIX promotes accumulation of γ-tubulin and thus facilitates efficient nucleation of astral MTs. In addition, ALIX promotes MT stability by recruiting microtubule-associated protein 1S (MAP1S), which stabilizes newly formed MTs. Altogether, our results demonstrate a novel evolutionarily conserved role of ALIX in providing robustness to the orientation of the MS by promoting astral MT formation during asymmetric and symmetric cell division.

KEYWORDS: ALIX , MAP1S, microtubule, mitotic spindle orientation, γ‐tubulin