Mitotic spindle orientation is intimately related to the anchoring of astral microtubules to the cell cortex. The mechanism regulating this mitotic process relies on the remodeling of the cell cortex and still includes many grey areas. In this study, we report that during early mitosis, annexin A2 (Anx2), a protein involved in cortical domain remodeling, recruits the scaffolding protein Ahnak to the cell cortex located near the spindle poles. This distribution is directly controlled by cell adhesion. Decreased expression of Anx2, or Ahnak, as well as altered cortical localization of Ahnak results in both delayed entry of cells into anaphase and unstable anchoring of the mitotic spindle, which results in altered spindle orientation. Furthermore, we observed that Ahnak is present in a complex with dynein-dynactin.
In prometaphase, Ahnak and Anx2 are required for the localization and cortical dynamics of dynein and NuMA. We therefore propose that the Ahnak/Anx2 complex influences the cortical organization of the astral microtubule anchoring complex, and thus the positioning of the mitotic spindle in human cells.