iASPP contributes to cortex rigidity, astral microtubule capture and mitotic spindle positioning

Abstract

The microtubule plus-end binding protein EB1 is the core of a complex protein network which regulates microtubule dynamics during important biological processes such as cell motility and mitosis. We found that iASPP, an inhibitor of p53 and predicted regulatory subunit of the PP1 phosphatase, associates with EB1 at microtubule plus-ends via a SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the leading edge of migrating cells, and at the cortex of mitotic cells leading to abnormal positioning of the mitotic spindle. These effects were recapitulated by the knockdown of Myosin-Ic (Myo1c), identified as a novel partner of iASPP. Moreover, iASPP or Myo1c knockdown cells failed to round up during mitosis because of defective cortical rigidity. We propose that iASPP, together with EB1 and Myo1c, contributes to mitotic cell cortex rigidity, allowing astral microtubule capture and appropriate positioning of the mitotic spindle.