iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning

iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning.

Aurélie Mangon (1, 2) , Danièle Salaün (1, 2) , Mohamed Lala Bouali (1, 2) , Mira Kuzmić (1, 2) , Sabine Quitard (1, 2) , Sylvie Thuault (1, 2) , Daniel Isnardon (1, 2) , Stéphane Audebert (1, 2) , Pierre-Henri Puech (3, 4) , Pascal Verdier-Pinard (1, 2) , Ali Badache (1, 2)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 IPC - Institut Paoli-Calmettes
3 LAI - Adhésion et Inflammation
4 Turing Center for Living Systems

iASPP is a protein mostly known as an inhibitor of p53 pro-apoptotic activity and a predicted regulatory subunit of the PP1 phosphatase, which is often overexpressed in tumors. We report that iASPP associates with the microtubule plus-end binding protein EB1, a central regulator of microtubule dynamics, via an SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the cortex of mitotic cells, leading to abnormal positioning of the mitotic spindle. These effects were recapitulated by the knockdown of the membrane-to-cortex linker Myosin-Ic (Myo1c), which we identified as a novel partner of iASPP. Moreover, iASPP or Myo1c knockdown cells failed to round up upon mitosis because of defective cortical stiffness. We propose that by increasing cortical rigidity, iASPP helps cancer cells maintain a spherical geometry suitable for proper mitotic spindle positioning and chromosome partitioning.

Domaines: Sciences du Vivant [q-bio]

Aurélie Mangon, Danièle Salaün, Mohamed Lala Bouali, Mira Kuzmić, Sabine Quitard, et al.. iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning. Journal of Cell Biology, 2021, 220 (12), ⟨10.1083/jcb.202012002⟩. ⟨hal-03623635⟩