Borg5 restricts contractility and motility in epithelial MDCK cells

Area of Science:

• Cell Biology
• Cytoskeletal Dynamics
• Epithelial Morphogenesis

Background:

• The Borg (Cdc42EP) protein family typically promotes septin-dependent contractility.
• Epithelial cell morphology is crucial for tissue function and is regulated by cytoskeletal dynamics.

Purpose of the Study:

• To investigate the role of epithelial Borg5 (Cdc42EP1) in Madin-Darby canine kidney (MDCK) cell monolayers.
• To elucidate the mechanism by which Borg5 influences cell contractility, adhesion, and morphology.

Main Methods:

• Depletion of Borg5 in MDCK cell monolayers.
• Analysis of F-actin cortex, stress fibers, and lamellae formation.
• Investigation of septin and myosin IIA (MYH9) interactions using co-localization and interaction studies.

Main Results:

• Borg5 depletion led to increased cell contractility, adhesion tension, and motility.
• Loss of Borg5 resulted in reduced lateral F-actin cortex and stimulated microtubule-dependent lamellae and radial stress fibers.
• Borg5 limits septin colocalization with microtubules and interacts with myosin IIA, counteracting septin-mediated myosin activation.

Conclusions:

• Epithelial Borg5 acts as a negative regulator of contractility, promoting isotropic cell shape in MDCK monolayers.
• Borg5 functions by modulating septin-microtubule and septin-myosin IIA interactions.
• These findings reveal a novel mechanism for controlling epithelial cell morphology and tissue organization.