Moesin controls cortical rigidity, cell rounding and spindle morphogenesis during mitosis

KUNDA, PATRICIA; PELLING, ANDREW; LIU, TAO; BAUM, BUZZ

Edimburgo

Congreso; Mechanics and Control of Citokinesis; 2008

During mitosis, animal cells undergo a complex sequence of morphological changes, from retraction of the cell margin and cell rounding at the onset of mitosis to axial elongation and cytokinesisat mitotic exit. Although later steps in this process are relatively well understood, the molecular mechanisms driving the early changes in mitotic cell form and their functional significance remain unknown. We identify DMoesin, the sole Drosophila member of the ERM family proteins, which crosslink F-actin to the cytoplasmic tails of plasma membrane proteins, as a key player.We show that DMoesin becomes activated and cortically localized following Slik-dependent phosphorylation at mitotic onset. This cortical pool of active Moesin induces cortical stiffening and cell rounding, and is sufficient to induce both processes in interphase cells, independently of Myosin II. Strikingly, the soft mitotic cells that lack Moesin exhibit profound defects in spindle morphogenesisand chromosome alignment, which can be rescued by re-establishing cortical tension from the outside the cell.These data show that the dynamic regulation of ERM protein activation and localisation during mitosis controls the establishmentof a stiff rounded cortex at metaphase, and facilitates polar relaxation at anaphase. Moreover changes in cortical rigidity are critical for the establishment and positioning of the mitotic spindle, for chromosome alignment and for orderly spindle elongation