Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons

• DOI: 10.1002/glia.23566
• Publication Date: 2018-11-28T18:23:17Z
• Authors: Andrej Adolf; Astrid Rohrbeck; Agnieszka Münster...; Malin Johansson; Hans‐Georg Kuhn; Marcel Alexander ...; Benedikt Brommer; Jan Markus Schwab; Ingo Just; Gudrun Ahnert‐Hilger; Markus Höltje
• Keywords: Internalization; Neuroglia; Intermediate Filament Protein

Abstract Clostridium botulinum C3 transferase (C3bot) ADP‐ribosylates rho proteins to change cellular functions in a variety of cell types including astrocytes and neurons. The intermediate filament protein vimentin as well transmembrane integrins are involved internalization C3bot into cells. exact contribution, however, these binding the surface subsequent uptake remains be unraveled. By comparing primary astrocyte cultures derived from wild‐type with Vim −/− mice, we demonstrate that lacking exhibited delayed ADP‐ribosylation rhoA concurrent blunted morphological response. This functional impairment was rescued by extracellular excess recombinant vimentin. Binding assays using harboring mutated integrin‐binding RGD motif (C3bot‐G89I) revealed involvement C3bot. Axonotrophic effects dependent postulate an underlying mechanism entertaining molecular cross‐talk between We present evidence for astrocytic release exosomes vitro scratch wound model. Exosomal vimentin+ particles released promote interaction neuronal membranes. effect vanished when culturing astrocytes. Specificity findings confirmed propagating enhanced synaptosomes rat spinal cord mouse brain. hypothesize reactive provide novel constituting axonotrophic (neuroprotective) plasticity augmenting after injury.