Misshapen coordinates protrusion restriction and actomyosin contractility during collective cell migration

Abstract

Collective cell migration is involved in development, wound healing and metastasis. In the Drosophila ovary, border cells (BC) form a small cluster that migrates collectively through the egg chamber. To achieve directed motility, the BC cluster coordinates the formation of protrusions in its leader cell and contractility at the rear. Restricting protrusions to leader cells requires the actin and plasma membrane linker Moesin. Herein, we show that the Ste20-like kinase Misshapen phosphorylates Moesin in vitro and in BC. Depletion of Misshapen disrupts protrusion restriction, thereby allowing other cells within the cluster to protrude. 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. Together, our results indicate that Misshapen is a key regulator of BC migration as it coordinates two independent pathways that restrict protrusion formation to the leader cells and induces contractile forces.

STRIPAK regulates Slik localization to control mitotic morphogenesis and epithelial integrity

“…S2, F and G ). Next, we immunoprecipitated endogenous Slik and measured its kinase activity in vitro on its natural substrate, the C-terminal part of moesin ( Plutoni et al, 2019 ). We found that the depletion of Strip, Cka, PP2A-29B, or Mts did not affect the kinase activity of Slik ( Fig.…”

ERM Proteins at the Crossroad of Leukocyte Polarization, Migration and Intercellular Adhesion

“…Moreover, recent attention has been given to germinal center kinases (GCK), a subfamily of the mammalian sterile 20-like kinases (Mst) including lymphocyte-oriented kinase (LOK), Mst4, SLK and Nck interacting kinase (NIK), as the main kinases that phosphorylate the regulatory Thr of ERMs during cell motility and division [46][47][48][49][50][51]. To this list of kinases, we must now add two sterile 20-like kinases identified in Drosophila, misshapen (an orthologue of NIK) and Slik/SLK [52][53][54].…”

“…On the other hand, taking advantage of the fact that moesin is the sole ERM member expressed in Drosophila, an important role for moesin in control of the leading pseudopod has been also associated with persistence and directionality of collective cell migration in vivo, a process by which groups of cells coordinately move through tissues [102]. In border cells of the egg chamber in the Drosophila ovary, which form a small cluster that migrates directionally by means of a pseudopod strictly formed at the front of the cluster's leader cell, silencing of moesin or the moesin kinase misshapen promotes formation of protrusions in non-leader cells and disturbs polarized migration of cell clusters [52,103], suggesting that localization of moesin at cell-cell contacts can foster formation of the leading pseudopod by increasing cortical membrane stiffness. In the immune system, most leukocytes move as solitary cells, but in certain lymphoid malignancies they can also move as aggregates in tissues [104].…”

Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress

“…Genetic screens have yielded insights into the molecular mechanisms that specify which of the ~850 follicle cells acquire the ability to migrate 5,6 , the developmental timing of the migration 7,8 , collective direction sensing, and cytoskeletal dynamics [9][10][11][12][13][14][15][16][17][18][19] . While much is understood, insights continue to emerge from border cell studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] . The gene catsup was identified both in a large-scale, ethyl methanesulfonate-induced mutagenesis screen for border cell migration defects in mosaic clones 35 and in a whole-genome gene expression profile 36 .…”