% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Schwenk:138865,
author = {Schwenk, Benjamin M and Hartmann, Hannelore and Serdaroglu,
Alperen and Schludi, Martin H and Hornburg, Daniel and
Meissner, Felix and Orozco, Denise and Colombo, Alessio and
Tahirovic, Sabina and Michaelsen, Meike and Schreiber,
Franziska and Haupt, Simone and Peitz, Michael and Brüstle,
Oliver and Küpper, Clemens and Klopstock, Thomas and Otto,
Markus and Ludolph, Albert C and Arzberger, Thomas and Kuhn,
Peer-Hendrik and Edbauer, Dieter},
title = {{TDP}-43 loss of function inhibits endosomal trafficking
and alters trophic signaling in neurons.},
journal = {The EMBO journal},
volume = {35},
number = {21},
issn = {0261-4189},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2020-05187},
pages = {2350-2370},
year = {2016},
abstract = {Nuclear clearance of TDP-43 into cytoplasmic aggregates is
a key driver of neurodegeneration in amyotrophic lateral
sclerosis (ALS) and frontotemporal lobar degeneration
(FTLD), but the mechanisms are unclear. Here, we show that
TDP-43 knockdown specifically reduces the number and
motility of RAB11-positive recycling endosomes in dendrites,
while TDP-43 overexpression has the opposite effect. This is
associated with delayed transferrin recycling in
TDP-43-knockdown neurons and decreased β2-transferrin
levels in patient CSF Whole proteome quantification
identified the upregulation of the ESCRT component VPS4B
upon TDP-43 knockdown in neurons. Luciferase reporter assays
and chromatin immunoprecipitation suggest that TDP-43
represses VPS4B transcription. Preventing VPS4B upregulation
or expression of its functional antagonist ALIX restores
trafficking of recycling endosomes. Proteomic analysis
revealed the broad reduction in surface expression of key
receptors upon TDP-43 knockdown, including ErbB4, the
neuregulin 1 receptor. TDP-43 knockdown delays the surface
delivery of ErbB4. ErbB4 overexpression, but not neuregulin
1 stimulation, prevents dendrite loss upon TDP-43 knockdown.
Thus, impaired recycling of ErbB4 and other receptors to the
cell surface may contribute to TDP-43-induced
neurodegeneration by blocking trophic signaling.},
keywords = {ATPases Associated with Diverse Cellular Activities /
Adenosine Triphosphatases: genetics / Adenosine
Triphosphatases: metabolism / Amyotrophic Lateral Sclerosis:
genetics / Amyotrophic Lateral Sclerosis: metabolism /
Animals / Cells, Cultured / DNA-Binding Proteins: genetics /
DNA-Binding Proteins: metabolism / Endosomal Sorting
Complexes Required for Transport: genetics / Endosomal
Sorting Complexes Required for Transport: metabolism /
Endosomes: metabolism / Frontotemporal Lobar Degeneration:
genetics / Frontotemporal Lobar Degeneration: metabolism /
Gene Knockdown Techniques / Hippocampus: cytology / Humans /
Neurons: metabolism / Protein Transport / Rats / Receptor,
ErbB-4: genetics / Receptor, ErbB-4: metabolism / Receptor,
Fibroblast Growth Factor, Type 1: metabolism / Signal
Transduction / CHMP2B protein, human (NLM Chemicals) /
DNA-Binding Proteins (NLM Chemicals) / Endosomal Sorting
Complexes Required for Transport (NLM Chemicals) / TDP-43
protein, human (NLM Chemicals) / ERBB4 protein, human (NLM
Chemicals) / FGFR1 protein, human (NLM Chemicals) /
Receptor, ErbB-4 (NLM Chemicals) / Receptor, Fibroblast
Growth Factor, Type 1 (NLM Chemicals) / Adenosine
Triphosphatases (NLM Chemicals) / ATPases Associated with
Diverse Cellular Activities (NLM Chemicals) / VPS4B protein,
human (NLM Chemicals)},
cin = {AG Edbauer / AG Lichtenthaler / AG Tahirovic / U Clinical
Researchers - Magdeburg / Cell Programming Unit / AG Levin},
ddc = {570},
cid = {I:(DE-2719)1110004 / I:(DE-2719)1110006 /
I:(DE-2719)1140003 / I:(DE-2719)7000000 / I:(DE-2719)1013013
/ I:(DE-2719)1111016},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27621269},
pmc = {pmc:PMC5090220},
doi = {10.15252/embj.201694221},
url = {https://pub.dzne.de/record/138865},
}