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

Author:

Ghézali Grégory12,Ribot Jérôme1,Curry Nathan3,Pillet Laure‐Elise14,Boutet‐Porretta Flora12,Mozheiko Daria12,Calvo Charles‐Félix1,Ezan Pascal1,Perfettini Isabelle5,Lecoin Laure1,Janel Sébastien6ORCID,Zapata Jonathan1,Escartin Carole7ORCID,Etienne‐Manneville Sandrine5,Kaminski Clemens F.3,Rouach Nathalie13ORCID

Affiliation:

1. Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife Université PSL Paris France

2. Doctoral School N° 158, Sorbonne Université Paris France

3. Department of Chemical Engineering and Biotechnology University of Cambridge Cambridge UK

4. Doctoral School N°562, Université Paris Cité Paris France

5. Institut Pasteur, Université de Paris, CNRS, Cell Polarity, Migration and Cancer Unit Paris France

6. Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, CIIL ‐ Center for Infection and Immunity of Lille Lille France

7. Université Paris‐Saclay, CEA, CNRS, MIRCen Laboratoire des Maladies Neurodégénératives Fontenay‐aux‐Roses France

Abstract

AbstractDuring 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.

Funder

Medical Research Council

Engineering and Physical Sciences Research Council

MSCA

FP7 Ideas: European Research Council

Publisher

Wiley

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