2024
Glia

Connexin 30 locally controls actin cytoskeleton and mechanical remodeling in motile astrocytes

Authors:

Grégory Ghézali, Jérôme Ribot, Nathan Curry, Laure-Elise Pillet, Flora Boutet-Porretta, Daria Mozheiko, Charles-Félix Calvo, Pascal Ezan, Isabelle Perfettini, Laure Lecoin, Sébastien Janel, Jonathan Zapata, Carole Escartin, Sandrine Etienne-Manneville, Clemens F. Kaminski, Nathalie Rouach

Keywords:

brain maturation; Connexin 30; cell migration; actin cytoskeleton; ; astrocytes; actin; plasticity

Abstract:

During brain maturation, astrocytes establish complex morphologies unveiling intense structural plasticity. Connexin 30 (Cx30), a gap-junction channel-forming protein expressed postnatally, dynamically regulates during development astrocyte morphological properties by controlling ramification and extension of fine processes. However, the underlying mechanisms remain unexplored. Here, we found in vitro that Cx30 interacts with the actin cytoskeleton in astrocytes and inhibits its structural reorganization and dynamics during cell migration. This translates into an alteration of local physical surface properties, as assessed by correlative imaging using stimulated emission depletion (STED) super resolution imaging and atomic force microscopy (AFM). Specifically, Cx30 impaired astrocyte cell surface topology and cortical stiffness in motile astrocytes. As Cx30 alters actin organization, dynamics, and membrane physical properties, we assessed whether it controls astrocyte migration. We found that Cx30 reduced persistence and directionality of migrating astrocytes. Altogether, these data reveal Cx30 as a brake for astrocyte structural and mechanical plasticity.