001     138865
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024 7 _ |a 10.15252/embj.201694221
|2 doi
024 7 _ |a pmid:27621269
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024 7 _ |a pmc:PMC5090220
|2 pmc
024 7 _ |a 0261-4189
|2 ISSN
024 7 _ |a 1460-2075
|2 ISSN
024 7 _ |a altmetric:11966839
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037 _ _ |a DZNE-2020-05187
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Schwenk, Benjamin M
|0 P:(DE-2719)2551184
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|e First author
|u dzne
245 _ _ |a TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons.
260 _ _ |a Hoboken, NJ [u.a.]
|c 2016
|b Wiley
264 _ 1 |3 online
|2 Crossref
|b EMBO
|c 2016-09-12
264 _ 1 |3 print
|2 Crossref
|b EMBO
|c 2016-11-02
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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542 _ _ |i 2016-09-12
|2 Crossref
|u http://creativecommons.org/licenses/by-nc-nd/4.0/
542 _ _ |i 2016-09-12
|2 Crossref
|u http://doi.wiley.com/10.1002/tdm_license_1.1
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650 _ 7 |a CHMP2B protein, human
|2 NLM Chemicals
650 _ 7 |a DNA-Binding Proteins
|2 NLM Chemicals
650 _ 7 |a Endosomal Sorting Complexes Required for Transport
|2 NLM Chemicals
650 _ 7 |a TDP-43 protein, human
|2 NLM Chemicals
650 _ 7 |a ERBB4 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a FGFR1 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Receptor, ErbB-4
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Receptor, Fibroblast Growth Factor, Type 1
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Adenosine Triphosphatases
|0 EC 3.6.1.-
|2 NLM Chemicals
650 _ 7 |a ATPases Associated with Diverse Cellular Activities
|0 EC 3.6.4.-
|2 NLM Chemicals
650 _ 7 |a VPS4B protein, human
|0 EC 3.6.4.6
|2 NLM Chemicals
650 _ 2 |a ATPases Associated with Diverse Cellular Activities
|2 MeSH
650 _ 2 |a Adenosine Triphosphatases: genetics
|2 MeSH
650 _ 2 |a Adenosine Triphosphatases: metabolism
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: metabolism
|2 MeSH
650 _ 2 |a Endosomal Sorting Complexes Required for Transport: genetics
|2 MeSH
650 _ 2 |a Endosomal Sorting Complexes Required for Transport: metabolism
|2 MeSH
650 _ 2 |a Endosomes: metabolism
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: genetics
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: metabolism
|2 MeSH
650 _ 2 |a Gene Knockdown Techniques
|2 MeSH
650 _ 2 |a Hippocampus: cytology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Protein Transport
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Receptor, ErbB-4: genetics
|2 MeSH
650 _ 2 |a Receptor, ErbB-4: metabolism
|2 MeSH
650 _ 2 |a Receptor, Fibroblast Growth Factor, Type 1: metabolism
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
700 1 _ |a Hartmann, Hannelore
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700 1 _ |a Serdaroglu, Alperen
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700 1 _ |a Schludi, Martin H
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700 1 _ |a Hornburg, Daniel
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700 1 _ |a Meissner, Felix
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700 1 _ |a Colombo, Alessio
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700 1 _ |a Tahirovic, Sabina
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700 1 _ |a Michaelsen, Meike
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700 1 _ |a Schreiber, Franziska
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700 1 _ |a Haupt, Simone
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700 1 _ |a Peitz, Michael
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700 1 _ |a Brüstle, Oliver
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700 1 _ |a Küpper, Clemens
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700 1 _ |a Klopstock, Thomas
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700 1 _ |a Otto, Markus
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700 1 _ |a Ludolph, Albert C
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700 1 _ |a Arzberger, Thomas
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700 1 _ |a Kuhn, Peer-Hendrik
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700 1 _ |a Edbauer, Dieter
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773 1 8 |a 10.15252/embj.201694221
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773 _ _ |a 10.15252/embj.201694221
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999 C 5 |9 -- missing cx lookup --
|a 10.1523/JNEUROSCI.19-16-07037.1999
|2 Crossref
|o 10.1523/JNEUROSCI.19-16-07037.1999
999 C 5 |9 -- missing cx lookup --
|a 10.1038/nn.2778
|2 Crossref
|o 10.1038/nn.2778
999 C 5 |9 -- missing cx lookup --
|a 10.4161/bioa.1.1.15173
|2 Crossref
|o 10.4161/bioa.1.1.15173
999 C 5 |9 -- missing cx lookup --
|a 10.1073/pnas.091062498
|2 Crossref
|o 10.1073/pnas.091062498
999 C 5 |9 -- missing cx lookup --
|a 10.1093/hmg/ddq100
|2 Crossref
|o 10.1093/hmg/ddq100
999 C 5 |9 -- missing cx lookup --
|a 10.1093/nar/gkv1145
|2 Crossref
|o 10.1093/nar/gkv1145
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-015-1460-x
|2 Crossref
|o 10.1007/s00401-015-1460-x
999 C 5 |9 -- missing cx lookup --
|a 10.1074/jbc.M112.359000
|2 Crossref
|o 10.1074/jbc.M112.359000
999 C 5 |9 -- missing cx lookup --
|a 10.15252/embj.201591998
|2 Crossref
|o 10.15252/embj.201591998
999 C 5 |9 -- missing cx lookup --
|a 10.1091/mbc.11.2.747
|2 Crossref
|o 10.1091/mbc.11.2.747


LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21