Ca²⁺ Release by IP₃ Receptors Is Required to Orient the Mitotic Spindle

The mitotic spindle distributes chromosomes evenly to daughter cells during mitosis. The orientation of the spindle, guided by internal and external cues, determines the axis of cell division and thereby contributes to tissue morphogenesis. Progression through mitosis requires local Ca²⁺ signals at critical steps, and because store-operated Ca²⁺ entry is inhibited during mitosis, those signals probably require Ca²⁺ release through inositol 1,4,5-trisphosphate receptors (IP₃Rs). In cells without IP₃Rs, astral microtubules around the daughter centrosome are shorter than those at the mother centrosome, and the mitotic spindle fails to align with the substratum during metaphase. The misalignment is due to the spindle ineffectively detecting internal cues rather than a failure of cells to recognize the substratum. Expression of type 3 IP₃R is sufficient to rescue spindle alignment, but only if the IP₃R has a functional pore. We conclude that Ca²⁺ signals evoked by IP₃Rs are required to orient the mitotic spindle.