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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/9796

Title: A 29-amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation
Authors: Hoeltje, Markus
Djalali, Susann
Hofmann, Fred
Muenster-Wandowski, Agnieszka
Hendrix, Sven
Boato, Francesco
Dreger, Stefanie C.
Grosse, Gisela
Henneberger, Christian
Grantyn, Rosemarie
Just, Ingo
Ahnert-Hilger, Gudrun
Issue Date: 2009
Citation: The FASEB journal, 23(4). p. 1115-1126
Abstract: 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 sub-micromolar concentrations. Several C3bot constructs, including the short peptide, enhanced the number of axonal segments from mid-to higher-order segments. C3bot(154-182) 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 C3bot(154-182) 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. Holtje, M., Djalali, S., Hofmann, F., Munster-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. FASEB J. 23, 1115-1126 (2009)
Notes: [Hoeltje, Markus] Charite Univ Med Berlin, Inst Integrat Neuroanat, Ctr Anat, AG Funkt Zellbiol, D-10115 Berlin, Germany. [Hendrix, Sven; Boato, Francesco] Charite Univ Med Berlin, Ctr Anat, Inst Zell & Neurobiol, D-10115 Berlin, Germany. [Henneberger, Christian; Grantyn, Rosemarie] Charite Univ Med Berlin, Johannes Muller Inst Neurophysiol, AG Entwicklungsphysiol, D-10115 Berlin, Germany. [Hofmann, Fred; Dreger, Stefanie C.; Just, Ingo] Hannover Med Sch, Inst Toxikol, D-30623 Hannover, Germany. [Hendrix, Sven] Hasselt Univ, Dept Morphol, Hasselt, Belgium. [Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Hasselt, Belgium.
URI: http://hdl.handle.net/1942/9796
DOI: 10.1096/fj.08-116855
ISI #: 000266651600015
ISSN: 0892-6638
Category: A1
Type: Journal Contribution
Validation: ecoom, 2010
Appears in Collections: Research publications

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