TGF-β 1 enhances neurite outgrowth via regulation of proteasome function and EFABP
Open accessAbstract
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-beta), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulates proteasome function in primary midbrain neurons. TGF-beta 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-beta 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-beta treatment and confirmed this finding by co-immunoprecipitation. While application of TGF-beta 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-beta, can result in an enrichment of proteins, such as EFABP, that mediate physiological functions, such as neurite regeneration.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of Smad2 signaling has also been reported to occur with myelin axonal growth inhibition, and direct activation of Smad2 reduces axonal outgrowth in some preparations.
“However, activation of Smad2 signaling has also been reported to occur with myelin axonal growth inhibition, and direct activation of Smad2 reduces axonal outgrowth in some preparations22,24.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [22]
In other in vitro systems, TGFβ promotes axonal outgrowth of injured neurons and blockade of TGFβRII alters neuronal polarity and leads to shorter axons.
“In other in vitro systems, TGFβ promotes axonal outgrowth of injured neurons21,22,39,40 and blockade of TGFβRII alters neuronal polarity and leads to shorter axons42.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [22]
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 55 · Cited by 50
- Authors
- Knöferle, J., Ramljak, S., Koch, J. C., Tönges, L., Asif, A. R., Michel, U., Wouters, F. S., Heermann, S., Krieglstein, K., Zerr, I., Bähr, M., & Lingor, P.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- University of Göttingen (DE)
- University of Freiburg (DE)
- Corresponding author
- Lingor, Paul
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 38
- Issue
- 3
- Pages
- 395-404
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2024385705
- Cited by
- 50
- References
- 55
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Repository of Futwangen University of Applied Sciences (Furtwangen University) (submittedVersion)
- GRO (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- TGF-β1, neurite outgrowth, proteasome function, ubiquitin-proteasome system, epidermal fatty acid binding protein, dopaminergic neurons, midbrain neurons, ubiquitinated proteins, chymotrypsin-like activity, neurite regeneration, Parkinson's disease
- MeSH terms
- Animals, Cells, Cultured, Dopamine, Eye Proteins, Hydrolysis, Mesencephalon, Nerve Regeneration, Nerve Tissue Proteins, Neurons, Time Factors, Neurites, Rats, Wistar, Proteasome Endopeptidase Complex, Cell Enlargement, Fatty Acid-Binding Proteins, Rats, Transforming Growth Factor beta1, Ubiquitination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
