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

Abstract

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.