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| Home > Publications Database > Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. > print |
| 001 | 136892 | ||
| 005 | 20240321220144.0 | ||
| 024 | 7 | _ | |a 10.1523/JNEUROSCI.3372-12.2013 |2 doi |
| 024 | 7 | _ | |a pmid:23637177 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC6618983 |2 pmc |
| 024 | 7 | _ | |a 0270-6474 |2 ISSN |
| 024 | 7 | _ | |a 1529-2401 |2 ISSN |
| 024 | 7 | _ | |a altmetric:41312032 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-03214 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Fleck, Daniel |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. |
| 260 | _ | _ | |a Washington, DC |c 2013 |b Soc.57413 |
| 264 | _ | 1 | |3 online |2 Crossref |b Society for Neuroscience |c 2013-05-01 |
| 264 | _ | 1 | |3 print |2 Crossref |b Society for Neuroscience |c 2013-05-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1589983214_10887 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Proteolytic shedding of cell surface proteins generates paracrine signals involved in numerous signaling pathways. Neuregulin 1 (NRG1) type III is involved in myelination of the peripheral nervous system, for which it requires proteolytic activation by proteases of the ADAM family and BACE1. These proteases are major therapeutic targets for the prevention of Alzheimer's disease because they are also involved in the proteolytic generation of the neurotoxic amyloid β-peptide. Identification and functional investigation of their physiological substrates is therefore of greatest importance in preventing unwanted side effects. Here we investigated proteolytic processing of NRG1 type III and demonstrate that the ectodomain can be cleaved by three different sheddases, namely ADAM10, ADAM17, and BACE1. Surprisingly, we not only found cleavage by ADAM10, ADAM17, and BACE1 C-terminal to the epidermal growth factor (EGF)-like domain, which is believed to play a pivotal role in signaling, but also additional cleavage sites for ADAM17 and BACE1 N-terminal to that domain. Proteolytic processing at N- and C-terminal sites of the EGF-like domain results in the secretion of this domain from NRG1 type III. The soluble EGF-like domain is functionally active and stimulates ErbB3 signaling in tissue culture assays. Moreover, the soluble EGF-like domain is capable of rescuing hypomyelination in a zebrafish mutant lacking BACE1. Our data suggest that NRG1 type III-dependent myelination is not only controlled by membrane-retained NRG1 type III, but also in a paracrine manner via proteolytic liberation of the EGF-like domain. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2013-11-01 |2 Crossref |u https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a NRG3 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Neuregulins |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA, Messenger |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA, Small Interfering |2 NLM Chemicals |
| 650 | _ | 7 | |a Epidermal Growth Factor |0 62229-50-9 |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid Precursor Protein Secretases |0 EC 3.4.- |2 NLM Chemicals |
| 650 | _ | 7 | |a Aspartic Acid Endopeptidases |0 EC 3.4.23.- |2 NLM Chemicals |
| 650 | _ | 7 | |a BACE1 protein, human |0 EC 3.4.23.46 |2 NLM Chemicals |
| 650 | _ | 7 | |a ADAM Proteins |0 EC 3.4.24.- |2 NLM Chemicals |
| 650 | _ | 7 | |a ADAM17 Protein |0 EC 3.4.24.86 |2 NLM Chemicals |
| 650 | _ | 7 | |a ADAM17 protein, human |0 EC 3.4.24.86 |2 NLM Chemicals |
| 650 | _ | 7 | |a Adam17 protein, rat |0 EC 3.4.24.86 |2 NLM Chemicals |
| 650 | _ | 2 | |a ADAM Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a ADAM17 Protein |2 MeSH |
| 650 | _ | 2 | |a Amyloid Precursor Protein Secretases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Aspartic Acid Endopeptidases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Cell Membrane: metabolism |2 MeSH |
| 650 | _ | 2 | |a Cells, Cultured |2 MeSH |
| 650 | _ | 2 | |a Cricetinae |2 MeSH |
| 650 | _ | 2 | |a Cricetulus |2 MeSH |
| 650 | _ | 2 | |a Embryo, Mammalian |2 MeSH |
| 650 | _ | 2 | |a Epidermal Growth Factor: analogs & derivatives |2 MeSH |
| 650 | _ | 2 | |a Epidermal Growth Factor: chemistry |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Immunoprecipitation |2 MeSH |
| 650 | _ | 2 | |a Neuregulins: genetics |2 MeSH |
| 650 | _ | 2 | |a Neuregulins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Neurons |2 MeSH |
| 650 | _ | 2 | |a Paracrine Communication: physiology |2 MeSH |
| 650 | _ | 2 | |a Phosphorylation |2 MeSH |
| 650 | _ | 2 | |a Proteolysis |2 MeSH |
| 650 | _ | 2 | |a RNA, Messenger: administration & dosage |2 MeSH |
| 650 | _ | 2 | |a RNA, Messenger: metabolism |2 MeSH |
| 650 | _ | 2 | |a RNA, Small Interfering: metabolism |2 MeSH |
| 650 | _ | 2 | |a Rats |2 MeSH |
| 650 | _ | 2 | |a Rats, Sprague-Dawley |2 MeSH |
| 650 | _ | 2 | |a Schwann Cells |2 MeSH |
| 650 | _ | 2 | |a Transfection |2 MeSH |
| 650 | _ | 2 | |a Zebrafish |2 MeSH |
| 700 | 1 | _ | |a van Bebber, Frauke |0 P:(DE-2719)9000319 |b 1 |
| 700 | 1 | _ | |a Colombo, Alessio |0 P:(DE-2719)2340744 |b 2 |
| 700 | 1 | _ | |a Galante, Chiara |b 3 |
| 700 | 1 | _ | |a Schwenk, Benjamin M |0 P:(DE-2719)2551184 |b 4 |
| 700 | 1 | _ | |a Rabe, Linnea |b 5 |
| 700 | 1 | _ | |a Hampel, Heike |b 6 |
| 700 | 1 | _ | |a Novak, Bozidar |b 7 |
| 700 | 1 | _ | |a Kremmer, Elisabeth |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Tahirovic, Sabina |0 P:(DE-2719)2442036 |b 9 |
| 700 | 1 | _ | |a Edbauer, Dieter |0 P:(DE-2719)2231621 |b 10 |
| 700 | 1 | _ | |a Lichtenthaler, Stefan F |0 P:(DE-2719)2181459 |b 11 |
| 700 | 1 | _ | |a Schmid, Bettina |0 P:(DE-2719)2241638 |b 12 |
| 700 | 1 | _ | |a Willem, Michael |0 P:(DE-HGF)0 |b 13 |
| 700 | 1 | _ | |a Haass, Christian |0 P:(DE-2719)2202037 |b 14 |e Last author |
| 773 | 1 | 8 | |a 10.1523/jneurosci.3372-12.2013 |b Society for Neuroscience |d 2013-05-01 |n 18 |p 7856-7869 |3 journal-article |2 Crossref |t The Journal of Neuroscience |v 33 |y 2013 |x 0270-6474 |
| 773 | _ | _ | |a 10.1523/JNEUROSCI.3372-12.2013 |g Vol. 33, no. 18, p. 7856 - 7869 |0 PERI:(DE-600)1475274-8 |n 18 |q 33:18<7856 - 7869 |p 7856-7869 |t The journal of neuroscience |v 33 |y 2013 |x 0270-6474 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618983 |
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| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |2 G:(DE-HGF)POF3-300 |v Disease Mechanisms and Model Systems |x 0 |
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| 920 | 1 | _ | |0 I:(DE-2719)1110007 |k AG Haass old |l ALS, FTLD and Zebrafish models |x 4 |
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