Abstract
The Borg (or Cdc42EP) family consists of septin-binding proteins that are known to promote septin-dependent stress fibers and acto-myosin contractility. We show here that epithelial Borg5 (also known as Cdc42EP1) instead limits contractility, cell-cell adhesion tension and motility, as is required for the acquisition of columnar, isotropic cell morphology in mature MDCK monolayers. Borg5 depletion inhibited the development of the lateral F-actin cortex and stimulated microtubule-dependent leading-edge lamellae as well as radial stress fibers and, independently of the basal F-actin phenotype, caused anisotropy of apical surfaces within compacted monolayers. We determined that Borg5 limits colocalization of septin proteins with microtubules, and that like septin 2, Borg5 interacts with the rod-domain of myosin IIA (herein referring to the MYH9 heavy chain). The interaction of myosin IIA with Borg5 was reduced in the presence of septins. Because septins also mediate myosin activation, we propose that Borg5 limits contractility in MDCK cells in part by counteracting septin-associated myosin activity.