Regulation of mitotic spindle orientation: an integrated view

Mitotic spindle orientation is essential for cell fate decisions, epithelial maintenance, and tissue morphogenesis. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. Early studies identified th...

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Bibliographic Details
Published in:EMBO reports 2016-08, Vol.17 (8), p.1106-1130
Main Authors: di Pietro, Florencia, Echard, Arnaud, Morin, Xavier
Format: Article
Language:English
Subjects:
actin cortex
Actins - metabolism
Animals
astral microtubules
Biochemistry
Biomechanical Phenomena
Biophysics
Cell Cycle
Cell division
cell geometry
Cellular biology
Dyneins - metabolism
EMBO06
Gene Expression Regulation
Genetics
Humans
Microtubules - metabolism
Mitosis
Multiprotein Complexes - metabolism
Nuclear Matrix-Associated Proteins - metabolism
NuMA
Protein Binding
Protein Stability
Protein Transport
Review
Reviews
Signal Transduction
Spindle Apparatus - metabolism
spindle orientation
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Summary:Mitotic spindle orientation is essential for cell fate decisions, epithelial maintenance, and tissue morphogenesis. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. Early studies identified the evolutionarily conserved Gαi/LGN/NuMA complex as a key regulator that polarizes cortical force generators. In recent years, a combination of genetics, biochemistry, modeling, and live imaging has contributed to decipher the mechanisms of spindle orientation. Here, we highlight the dynamic nature of the assembly of this complex and discuss the molecular regulation of its localization. Remarkably, a number of LGN‐independent mechanisms were described recently, whereas NuMA remains central in most pathways involved in recruiting force generators at the cell cortex. We also describe the emerging role of the actin cortex in spindle orientation and discuss how dynamic astral microtubule formation is involved. We further give an overview on instructive external signals that control spindle orientation in tissues. Finally, we discuss the influence of cell geometry and mechanical forces on spindle orientation. Graphical Abstract Mitotic spindle orientation is important for fate decisions, epithelial maintenance, and tissue morphogenesis. This review highlights the dynamic nature of spindle assembly and discusses the molecular regulation of its localization and external signals that control its orientation.
ISSN:1469-221X
1469-3178
DOI:10.15252/embr.201642292