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29-amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation

Höltje, Markus ; Djalali, Susann ; Hofmann, Fred ; Münster-Wandowski, Agnieszka ; Hendrix, Sven ; Boato, Francesco ; Dreger, Stefanie C ; Grosse, Gisela ; Henneberger, Christian ; Grantyn, Rosemarie ; Just, Ingo ; Ahnert-Hilger, Gudrun

The FASEB journal, 2009-04, Vol.23 (4), p.1115-1126 [Periódico revisado por pares]

United States: The Federation of American Societies for Experimental Biology

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Título:
29-amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation
Autor: Höltje, Markus ; Djalali, Susann ; Hofmann, Fred ; Münster-Wandowski, Agnieszka ; Hendrix, Sven ; Boato, Francesco ; Dreger, Stefanie C ; Grosse, Gisela ; Henneberger, Christian ; Grantyn, Rosemarie ; Just, Ingo ; Ahnert-Hilger, Gudrun
Assuntos: ADP Ribose Transferases - chemistry ; ADP Ribose Transferases - genetics ; ADP Ribose Transferases - metabolism ; Amino Acids - chemistry ; Amino Acids - pharmacology ; Animals ; axon ; Axons - drug effects ; Axons - metabolism ; Axons - physiology ; Biomarkers - metabolism ; Botulinum Toxins - chemistry ; Botulinum Toxins - genetics ; Botulinum Toxins - metabolism ; Cells, Cultured ; Clostridium botulinum - genetics ; Clostridium botulinum - metabolism ; Coculture Techniques ; Dendrites - drug effects ; Dendrites - genetics ; Dendrites - metabolism ; Dendrites - physiology ; Embryo, Mammalian ; Glutathione Transferase - metabolism ; Green Fluorescent Proteins - metabolism ; hippocampus ; Hippocampus - cytology ; Hippocampus - embryology ; Immunohistochemistry ; Mice ; Mice, Inbred Strains ; Microtubule-Associated Proteins - metabolism ; Molecular Weight ; Neurofilament Proteins - chemistry ; Neurofilament Proteins - metabolism ; Neurons - drug effects ; Neurons - metabolism ; Neurons - physiology ; Recombinant Proteins - chemistry ; Recombinant Proteins - isolation & purification ; Recombinant Proteins - metabolism ; regeneration ; Time Factors
É parte de: The FASEB journal, 2009-04, Vol.23 (4), p.1115-1126
Descrição: Small GTPases of the Rho family play versatile roles in the formation and development of axons and dendrites, effects often studied by the Rho-inactivating C3 transferase (C3bot) from Clostridium botulinum. Recently, we reported that transferase-deficient C3bot also exerted axonotrophic activity. Using overlapping peptides from the C3bot sequence, we identified a small peptide of 29 amino acids (covering residues 154-182) from the C-terminal region of C3bot that promotes both axonal and dendritic growth, as well as branching of hippocampal neurons, at submicromolar concentrations. Several C3bot constructs, including the short peptide, enhanced the number of axonal segments from mid- to higher-order segments. C3bot¹⁵⁴⁻¹⁸² also increased the number of synaptophysin-expressing terminals, up-regulated various synaptic proteins, and functionally increased the glutamate uptake. Staining against the vesicular glutamate and GABA transporters further revealed that the effect was attributable to a higher number of glutamatergic and GABAergic inputs on proximal dendrites of enhanced green fluorescent protein (EGFP)-transfected neurons. Using organotypical slice cultures, we also detected trophic effects of C3bot¹⁵⁴⁻¹⁸² on length and density of outgrowing fibers from the entorhinal cortex that were comparable to the effects elicited by full-length C3bot. In addition, an enhanced reinnervation was observed in a hippocampal-entorhinal lesion model. In summary, the neurotrophic effect of C3bot is executed by a C-terminal peptide fragment covering aa 154-182 of C3; it triggers dendritic and axonal growth and branching as well as increased synaptic connectivity. In contrast to full-length C3, this C3 peptide selectively acts on neurons but not on glial cells. Höltje, M., Djalali, S., Hofmann, F., Münster-Wandowski, A., Hendrix, S., Boato, F., Dreger, S. C., Grosse, G., Henneberger, C., Grantyn, R., Just, I., Ahnert-Hilger, G. A 29-amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation.
Editor: United States: The Federation of American Societies for Experimental Biology
Idioma: Inglês

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29-amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation

Höltje, Markus ; Djalali, Susann ; Hofmann, Fred ; Münster-Wandowski, Agnieszka ; Hendrix, Sven ; Boato, Francesco ; Dreger, Stefanie C ; Grosse, Gisela ; Henneberger, Christian ; Grantyn, Rosemarie ; Just, Ingo ; Ahnert-Hilger, Gudrun

United States: The Federation of American Societies for Experimental Biology

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