{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:09:34Z","timestamp":1773007774880,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Small GTPases of the Rho family play versatile roles in the formation and development of axons and dendrites, effects often studied by the Rho\u2010inactivating C3 transferase (C3bot) from\n                    <jats:italic>Clostridium botulinum<\/jats:italic>\n                    . Recently, we reported that transferasedeficient C3bot also exerted axonotrophic activity. Using overlapping peptides from the C3bot sequence, we identified a small peptide of 29 amino acids (covering residues 154\u2010182) from the C\u2010terminal region of C3bot that promotes both axonal and dendritic growth, as well as branching of hippocampal neurons, at sub\u2010micromolar concentrations. Several C3bot constructs, including the short peptide, enhanced the number of axonal segments from mid\u2010 to higher\u2010order segments. C3bot\n                    <jats:sup>154\u2010182<\/jats:sup>\n                    also increased the number of synaptophysin\u2010expressing terminals, up\u2010regulated 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)\u2010transfected neurons. Using organotypical slice cultures, we also detected trophic effects of C3bot\n                    <jats:sup>154\u2010182<\/jats:sup>\n                    on length and density of outgrowing fibers from the entorhinal cortex that were comparable to the effects elicited by full\u2010length C3bot. In addition, an enhanced reinnervation was observed in a hippocampal\u2010entorhinal lesion model. In summary, the neurotrophic effect of C3bot is executed by a C\u2010terminal peptide fragment covering aa 154\u2010182 of C3; it triggers dendritic and axonal growth and branching as well as increased synaptic connectivity. In contrast to full\u2010length C3, this C3 peptide selectively acts on neurons but not on glial cells. Holtje, M., Djalali, S., Hofmann, F., Munster\u2010Wandowski, A., Hendrix, S., Boato, F., Dreger, S. C., Gro\u00dfe, G., Henneberger, C., Grantyn, R., Just, I., Ahnert\u2010Hilger, G. A 29\u2010amino acid fragment of Clostridium botulinum C3 protein enhances neuronal outgrowth, connectivity, and reinnervation.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 23, 1115\u20131126 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-116855","type":"journal-article","created":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T20:54:32Z","timestamp":1228164872000},"page":"1115-1126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A 29\u2010amino acid fragment of\n                    <i>Clostridium botulinum<\/i>\n                    C3 protein enhances neuronal outgrowth, connectivity, and reinnervation"],"prefix":"10.1096","volume":"23","author":[{"given":"Markus","family":"H\u00f6ltje","sequence":"first","affiliation":[{"name":"Centrum f\u00fcr Anatomie AG Funktionelle Zellbiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susann","family":"Djalali","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie AG Funktionelle Zellbiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Toxikologie der Medizinischen Hochschule Hannover Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"M\u00fcnster-Wandowski","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie AG Funktionelle Zellbiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie Institut f\u00fcr Zell- und Neurobiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"},{"name":"Department of Morphology and Biomedical Research Institute (BIOMED) Hasselt University Hasselt Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Boato","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie Institut f\u00fcr Zell- und Neurobiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie C.","family":"Dreger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Toxikologie der Medizinischen Hochschule Hannover Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela","family":"Gro\u00dfe","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie AG Funktionelle Zellbiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Henneberger","sequence":"additional","affiliation":[{"name":"Johannes M\u00fcller Institut f\u00fcr Neurophysiologie, AG Entwicklungsphysiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemarie","family":"Grantyn","sequence":"additional","affiliation":[{"name":"Johannes M\u00fcller Institut f\u00fcr Neurophysiologie, AG Entwicklungsphysiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Just","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Toxikologie der Medizinischen Hochschule Hannover Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudrun","family":"Ahnert-Hilger","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Anatomie AG Funktionelle Zellbiologie Charit\u00e9-Universitatsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.cellbio.18.031802.150501","article-title":"Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity","volume":"18","author":"Luo L.","year":"2002","journal-title":"Annu. Rev. CellDev. Biol."},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.06.003"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1256405"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1128\/MCB.24.4.1736-1746.2004","article-title":"Human CNK1 acts as a scaffold protein, linking Rho and Ras signal transduction pathways","volume":"4","author":"Jaffe A. B.","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4084-06.2006"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00210-006-0113-y","article-title":"C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins","volume":"5","author":"Vogelsgesang M.","year":"2007","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2774-04.2004"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3931-04.2005"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.008"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03084"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210149"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02475.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4209-05.2006"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.06.044"},{"key":"e_1_2_5_16_1","doi-asserted-by":"crossref","first-page":"7189","DOI":"10.1523\/JNEUROSCI.5474-05.2006","article-title":"Altered balance of glutamatergic\/GABAergic synaptic input and associated changes in dendrite morphology after BDNF expression in BDNF-deficient hippocampal neurons","volume":"27","author":"Singh B.","year":"2006","journal-title":"J. Neurosci."},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neures.2007.05.011","article-title":"S100B modulates IL-6 release and cytotoxicity from hypothermic brain cells and inhibits hypothermia-induced axonal outgrowth","volume":"1","author":"Schmitt K. R.","year":"2007","journal-title":"Neurosci. Res."},{"key":"e_1_2_5_18_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/mcne.1999.0818","article-title":"Sema3C and netrin-1 differentially affect axon growth in the hippocampal formation","volume":"2","author":"Steup A.","year":"2000","journal-title":"Mol. Cell. Neurosci."},{"key":"e_1_2_5_19_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.brainresrev.2006.01.005","article-title":"Green-fluorescent-protein-expressing mice as models for the study of axonal growth and regeneration in vitro","volume":"1","author":"Hechler D.","year":"2006","journal-title":"Brain Res. Rev."},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1111\/j.1471-4159.2005.03443.x","article-title":"Role of Rho GTPase in astrocyte morphology and migratory response during in vitro wound healing","volume":"5","author":"Holtje M.","year":"2005","journal-title":"J. Neurochem."},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20687"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10400"},{"key":"e_1_2_5_23_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1006\/exnr.2001.7648","article-title":"Regeneration of entorhinal fibers in mouse slice cultures is age dependent and can be stimulated by NT-4, GDNF, and modulators of G-proteins and protein kinase C","volume":"1","author":"Prang P.","year":"2001","journal-title":"Exp. Neurol."},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403945200"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200305098"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123654"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.39.27407"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4292"},{"key":"e_1_2_5_29_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nsmb818","article-title":"How bacterial ADP-ribosylating toxins recognize substrates","volume":"9","author":"Sun J.","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"e_1_2_5_30_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1471-4159.2004.02779.x","article-title":"An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons","volume":"4","author":"Neiiendam J. L.","year":"2004","journal-title":"J. Neurochem."},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4322-04.2005"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1046\/j.0953-816x.2001.01506.x","article-title":"BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA(A) receptor surface expression","volume":"7","author":"Br\u00fcnig I.","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"e_1_2_5_33_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mcn.2006.10.005","article-title":"Interactive effects of C3, cyclic AMP and ciliary neurotrophic factor on adult retinal ganglion cell survival and axonal regeneration","volume":"1","author":"Hu Y.","year":"2007","journal-title":"Mol. Cell. Neurosci."},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706499200"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20466"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1436"},{"key":"e_1_2_5_37_1","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/sj.embor.7400826","article-title":"The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model","volume":"11","author":"Jokic N.","year":"2006","journal-title":"EMBO Rep."}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.08-116855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.08-116855","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.08-116855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:23:45Z","timestamp":1761693825000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.08-116855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1096\/fj.08-116855"],"URL":"https:\/\/doi.org\/10.1096\/fj.08-116855","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12]]},"assertion":[{"value":"2008-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}