TGF-β 1 enhances neurite outgrowth via regulation of proteasome function and EFABP
Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-β), a multifunctional cytokine and trophic factor for dopaminergic (DAer...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
6 March 2010
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| In: |
Neurobiology of disease
Year: 2010, Volume: 38, Issue: 3, Pages: 395-404 |
| ISSN: | 1095-953X |
| DOI: | 10.1016/j.nbd.2010.02.011 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.nbd.2010.02.011 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0969996110000598 
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| Author Notes: | Johanna Knöferle, Sanja Ramljak, Jan C. Koch, Lars Tönges, Abdul R. Asif, Uwe Michel, Fred S. Wouters, Stephan Heermann, Kerstin Krieglstein, Inga Zerr, Mathias Bähr, Paul Lingor |
| Summary: | Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-β), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulates proteasome function in primary midbrain neurons. TGF-β differentially inhibited proteasomal subactivities with a most pronounced time-dependent inhibition of the peptidyl-glutamyl peptide hydrolyzing-like and chymotrypsin-like subactivity. Regulation of proteasomal activity could be specifically quantified in the DAergic subpopulation. Protein blot analysis revealed an accumulation of ubiquitinated proteins after TGF-β treatment. The identity of these enriched proteins was further analyzed by 2D-gel electrophoresis and mass spectrometry. We found epidermal fatty acid binding protein (EFABP) to be strongly increased and ubiquitinated after TGF-β treatment and confirmed this finding by co-immunoprecipitation. While application of TGF-β increased neurite regeneration in a scratch lesion model, downregulation of EFABP by siRNA significantly decreased this effect. We thus postulate that a differential regulation of proteasomal function, as demonstrated for TGF-β, can result in an enrichment of proteins, such as EFABP, that mediate physiological functions, such as neurite regeneration. |
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| Item Description: | Gesehen am 21.06.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1095-953X |
| DOI: | 10.1016/j.nbd.2010.02.011 |