PP1-mediated moesin dephosphorylation couples polar relaxation to mitotic exit.
Animal cells undergo dramatic actin-dependent changes in shape as they progress through mitosis; they round up upon mitotic entry and elongate during chromosome segregation before dividing into two [1-3]. Moesin, the sole Drosophila ERM-family protein [4], plays a critical role in this process, through the construction of a stiff, rounded metaphase cortex [5-7]. At mitotic exit, this rigid cortex must be dismantled to allow for anaphase elongation and cytokinesis through the loss of the active pool of phospho-Thr559moesin from cell poles. Here, in an RNA interference (RNAi) screen for phosphatases involved in the temporal and spatial control of moesin, we identify PP1-87B RNAi as having elevated p-moesin levels and reduced cortical compliance. In mitosis, RNAi-induced depletion of PP1-87B or depletion of a conserved noncatalytic PP1 phosphatase subunit Sds22 leads to defects in p-moesin clearance from cell poles at anaphase, a delay in anaphase elongation, together with defects in bipolar anaphase relaxation and cytokinesis. Importantly, similar cortical defects are seen at anaphase following the expression of a constitutively active, phosphomimetic version of moesin. These data reveal a new role for the PP1-87B/Sds22 phosphatase, an important regulator of the metaphase-anaphase transition, in coupling moesin-dependent cell shape changes to mitotic exit.
MRC-Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Patricia
P
Kunda
Nelio T L
NT
Rodrigues
Emadaldin
E
Moeendarbary
Tao
T
Liu
Aleksandar
A
Ivetic
Guillaume
G
Charras
Buzz
B
Baum
D000818:Animals; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000166:cytology*; D008565:Membrane Proteins / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference
D008565:Membrane Proteins; C099886:moesin, Drosophila; D054645:Protein Phosphatase 1