PgmNr D1025: Inhibition of Protein Phosphatase 1 activity switches border cells from a collective to single cell mode of migration.

Authors:
J. A. McDonald 1 ; D. Ramel 2 ; G. Aranjuez 3 ; A. Burtscher 3 ; K. Sawant 1 ; X. Wang 2


Institutes
1) Division of Biology, Kansas State University, Manhattan, KS; 2) LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, France; 3) Lerner Research Institute, Cleveland Clinic, Cleveland, OH.


Keyword: cell migration

Abstract:

Cells often migrate in distinctly organized groups, or ‘collectives’, to form, remodel and sculpt tissues and organs. The mechanisms underlying how cells in collectives stay together and coordinate their movement rather than migrate as individual cells are still poorly understood. Drosophila border cells undergo collective cell migration during oogenesis. Border cells travel as a cohesive cluster of 6-10 cells between the large nurse cells to reach the oocyte. While several serine-threonine kinases and their target proteins have known roles in border cell migration, the functions of serine-threonine phosphatases are unknown. Here we show that Protein Phosphatase 1 (PP1) maintains the collective cohesion and migration of border cells. Inhibition of PP1 activity, either through the endogenous inhibitor NiPP1 or by knockdown of multiple PP1 catalytic subunits, causes border cells to round up and completely dissociate from the cluster while they are migrating. These individual border cells have altered motility, with protrusion formation between cells, and slower movement. Rac activity is still enriched in the leading border cell, showing that guidance signaling and directionality are not affected. However, levels of E-cadherin between cells are strongly reduced. Moreover, myosin localization is altered and F-actin becomes enriched around individual border cells rather than at the periphery of the entire border cell cluster. Together, these cellular alterations contribute to the inability of PP1-inhibited border cells to adhere tightly to each other and move as a group. Thus, PP1 activity promotes a collective rather than individual cell migration mode.