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Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics
Author(s) -
Malerød Lene,
Le Borgne Roland,
LieJensen Anette,
Eikenes Åsmund Husabø,
Brech Andreas,
Liestøl Knut,
Stenmark Harald,
Haglund Kaisa
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797741
Subject(s) - biology , astral microtubules , microbiology and biotechnology , spindle apparatus , mitosis , microtubule , centrosome , spindle pole body , dynamics (music) , kinetochore , cell division , genetics , physics , chromosome , cell , cell cycle , acoustics , gene
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 ( MT s), which results in abnormal MS orientation. Specifically, ALIX is recruited to the PCM via Drosophila Spindle defective 2 ( DS pd‐2)/Cep192, where ALIX promotes accumulation of γ‐tubulin and thus facilitates efficient nucleation of astral MT s. In addition, ALIX promotes MT stability by recruiting microtubule‐associated protein 1S ( MAP 1S), which stabilizes newly formed MT s. 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.