Regulation of mitotic spindle orientation: an integrated view

• 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
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201642292

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.