Misshapen coordinates protrusion restriction and actomyosin contractility during collective cell migration

Greg Emery
Institute for Research in Immunology and Cancer
Thursday, June 14, 2018 - 2:00pm
Ramsay Wright Building, Room 432
PhD Exam Seminar
Collective cell migration is a fundamental process involved in development, wound healing and metastasis. In the Drosophila ovary, border cells form a small cluster that migrates collectively through the egg chamber. To achieve directed motility, the border cell cluster must coordinate the formation of protrusions in their leader cell and contractility at the rear. The mechanism that restricts protrusions to leader cells requires the activity of the actin and plasma membrane linker Moesin. Herein, we show that the Ste20-like kinase Misshapen phosphorylates Moesin in vitro and in border cells. Depletion of Misshapen disrupts this protrusion restriction mechanism, thereby allowing other cells within the cluster to protrude as well. In addition, we show that Misshapen is critical to generate contractile forces both at the rear of the cluster and at the base of protrusions. Importantly, we find that in Misshapen-depleted clusters, expression of constitutively active forms of Moesin or Rok kinase restores protrusion restriction and contractility, respectively. Together, our results indicate that Misshapen is a master regulator of border cell migration as it coordinates two independent pathways that restrict protrusion formation to the leader cells and induces contractile forces.
Professor Rodrigo Fernandez-Gonzalez
Dept of Cell and Systems Biology