Your browser doesn't support javascript.
loading
Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons.
Adolf, Andrej; Rohrbeck, Astrid; Münster-Wandowski, Agnieszka; Johansson, Malin; Kuhn, Hans-Georg; Kopp, Marcel Alexander; Brommer, Benedikt; Schwab, Jan Markus; Just, Ingo; Ahnert-Hilger, Gudrun; Höltje, Markus.
Afiliação
  • Adolf A; Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Rohrbeck A; Institute of Toxicology, Hannover Medical School (MHH), Hanover, Germany.
  • Münster-Wandowski A; Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Johansson M; Department of Clinical Neuroscience at Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
  • Kuhn HG; Department of Clinical Neuroscience at Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
  • Kopp MA; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Brommer B; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Schwab JM; Berlin Institute of Health, QUEST - Center for Transforming Biomedical Research, Berlin, Germany.
  • Just I; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Ahnert-Hilger G; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Höltje M; Paraplegiology (Spinal Cord Injury Division), Belford Spinal Cord Injury Center, Departments of Neurology, Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
Glia ; 67(4): 703-717, 2019 04.
Article em En | MEDLINE | ID: mdl-30485542
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 as transmembrane integrins are involved in internalization of C3bot into cells. The exact contribution, however, of these proteins to binding of C3bot to the cell surface and subsequent cellular uptake remains to be unraveled. By comparing primary astrocyte cultures derived from wild-type with Vim-/- mice, we demonstrate that astrocytes lacking vimentin exhibited a delayed ADP-ribosylation of rhoA concurrent with a blunted morphological response. This functional impairment was rescued by the extracellular excess of recombinant vimentin. Binding assays using C3bot harboring a mutated integrin-binding RGD motif (C3bot-G89I) revealed the involvement of integrins in astrocyte binding of C3bot. Axonotrophic effects of C3bot are vimentin dependent and postulate an underlying mechanism entertaining a molecular cross-talk between astrocytes and neurons. We present functional evidence for astrocytic release of vimentin by exosomes using an in vitro scratch wound model. Exosomal vimentin+ particles released from wild-type astrocytes promote the interaction of C3bot with neuronal membranes. This effect vanished when culturing Vim-/- astrocytes. Specificity of these findings was confirmed by recombinant vimentin propagating enhanced binding of C3bot to synaptosomes from rat spinal cord and mouse brain. We hypothesize that vimentin+ exosomes released by reactive astrocytes provide a novel molecular mechanism constituting axonotrophic (neuroprotective) and plasticity augmenting effects of C3bot after spinal cord injury.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vimentina / Toxinas Botulínicas / Astrócitos / ADP Ribose Transferases / Vesículas Extracelulares / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vimentina / Toxinas Botulínicas / Astrócitos / ADP Ribose Transferases / Vesículas Extracelulares / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article