000136656 001__ 136656
000136656 005__ 20250324113224.0
000136656 0247_ $$2doi$$a10.1007/s00401-012-1020-6
000136656 0247_ $$2pmid$$apmid:22842875
000136656 0247_ $$2ISSN$$a0001-6322
000136656 0247_ $$2ISSN$$a1432-0533
000136656 0247_ $$2altmetric$$aaltmetric:929766
000136656 037__ $$aDZNE-2020-02978
000136656 041__ $$aEnglish
000136656 082__ $$a610
000136656 1001_ $$0P:(DE-2719)2810592$$aNeumann, Manuela$$b0$$eFirst author
000136656 245__ $$aTransportin 1 accumulates specifically with FET proteins but no other transportin cargos in FTLD-FUS and is absent in FUS inclusions in ALS with FUS mutations.
000136656 260__ $$aHeidelberg$$bSpringer$$c2012
000136656 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2012-07-28
000136656 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2012-11-01
000136656 3367_ $$2DRIVER$$aarticle
000136656 3367_ $$2DataCite$$aOutput Types/Journal article
000136656 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1742812303_20706
000136656 3367_ $$2BibTeX$$aARTICLE
000136656 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000136656 3367_ $$00$$2EndNote$$aJournal Article
000136656 520__ $$aAccumulation of the DNA/RNA binding protein fused in sarcoma (FUS) as inclusions in neurons and glia is the pathological hallmark of amyotrophic lateral sclerosis patients with mutations in FUS (ALS-FUS) as well as in several subtypes of frontotemporal lobar degeneration (FTLD-FUS), which are not associated with FUS mutations. Despite some overlap in the phenotype and neuropathology of FTLD-FUS and ALS-FUS, significant differences of potential pathomechanistic relevance were recently identified in the protein composition of inclusions in these conditions. While ALS-FUS showed only accumulation of FUS, inclusions in FTLD-FUS revealed co-accumulation of all members of the FET protein family, that include FUS, Ewing's sarcoma (EWS) and TATA-binding protein-associated factor 15 (TAF15) suggesting a more complex disturbance of transportin-mediated nuclear import of proteins in FTLD-FUS compared to ALS-FUS. To gain more insight into the mechanisms of inclusion body formation, we investigated the role of Transportin 1 (Trn1) as well as 13 additional cargo proteins of Transportin in the spectrum of FUS-opathies by immunohistochemistry and biochemically. FUS-positive inclusions in six ALS-FUS cases including four different mutations did not label for Trn1. In sharp contrast, the FET-positive pathology in all FTLD-FUS subtypes was also strongly labeled for Trn1 and often associated with a reduction in the normal nuclear staining of Trn1 in inclusion bearing cells, while no biochemical changes of Trn1 were detectable in FTLD-FUS. Notably, despite the dramatic changes in the subcellular distribution of Trn1 in FTLD-FUS, alterations of its cargo proteins were restricted to FET proteins and no changes in the normal physiological staining of 13 additional Trn1 targets, such as hnRNPA1, PAPBN1 and Sam68, were observed in FTLD-FUS. These data imply a specific dysfunction in the interaction between Trn1 and FET proteins in the inclusion body formation in FTLD-FUS. Moreover, the absence of Trn1 in ALS-FUS provides further evidence that ALS-FUS and FTLD-FUS have different underlying pathomechanisms.
000136656 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000136656 542__ $$2Crossref$$i2012-07-28$$uhttp://www.springer.com/tdm
000136656 588__ $$aDataset connected to CrossRef, PubMed,
000136656 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing
000136656 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000136656 650_7 $$2NLM Chemicals$$aHeterogeneous Nuclear Ribonucleoprotein A1
000136656 650_7 $$2NLM Chemicals$$aHeterogeneous-Nuclear Ribonucleoprotein Group A-B
000136656 650_7 $$2NLM Chemicals$$aKHDRBS1 protein, human
000136656 650_7 $$2NLM Chemicals$$aPABPN1 protein, human
000136656 650_7 $$2NLM Chemicals$$aPoly(A)-Binding Protein I
000136656 650_7 $$2NLM Chemicals$$aRNA-Binding Protein EWS
000136656 650_7 $$2NLM Chemicals$$aRNA-Binding Protein FUS
000136656 650_7 $$2NLM Chemicals$$aRNA-Binding Proteins
000136656 650_7 $$2NLM Chemicals$$aTAF15 protein, human
000136656 650_7 $$2NLM Chemicals$$aTATA-Binding Protein Associated Factors
000136656 650_7 $$2NLM Chemicals$$aTNPO1 protein, human
000136656 650_7 $$2NLM Chemicals$$abeta Karyopherins
000136656 650_7 $$2NLM Chemicals$$ahnRNPA1 protein, human
000136656 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: metabolism
000136656 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000136656 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: metabolism
000136656 650_2 $$2MeSH$$aBrain: metabolism
000136656 650_2 $$2MeSH$$aBrain: pathology
000136656 650_2 $$2MeSH$$aDNA-Binding Proteins: metabolism
000136656 650_2 $$2MeSH$$aFemale
000136656 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: genetics
000136656 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: metabolism
000136656 650_2 $$2MeSH$$aGene Expression Regulation: genetics
000136656 650_2 $$2MeSH$$aHeterogeneous Nuclear Ribonucleoprotein A1
000136656 650_2 $$2MeSH$$aHeterogeneous-Nuclear Ribonucleoprotein Group A-B: metabolism
000136656 650_2 $$2MeSH$$aHumans
000136656 650_2 $$2MeSH$$aInclusion Bodies: metabolism
000136656 650_2 $$2MeSH$$aInclusion Bodies: pathology
000136656 650_2 $$2MeSH$$aMale
000136656 650_2 $$2MeSH$$aMutation: genetics
000136656 650_2 $$2MeSH$$aPoly(A)-Binding Protein I: metabolism
000136656 650_2 $$2MeSH$$aRNA-Binding Protein EWS: metabolism
000136656 650_2 $$2MeSH$$aRNA-Binding Protein FUS: genetics
000136656 650_2 $$2MeSH$$aRNA-Binding Protein FUS: metabolism
000136656 650_2 $$2MeSH$$aRNA-Binding Proteins: metabolism
000136656 650_2 $$2MeSH$$aTATA-Binding Protein Associated Factors: metabolism
000136656 650_2 $$2MeSH$$abeta Karyopherins: metabolism
000136656 7001_ $$0P:(DE-2719)2810632$$aValori, Chiara Flora$$b1$$udzne
000136656 7001_ $$aAnsorge, Olaf$$b2
000136656 7001_ $$0P:(DE-2719)9000168$$aKretzschmar, Hans$$b3$$udzne
000136656 7001_ $$aMunoz, David G$$b4
000136656 7001_ $$aKusaka, Hirofumi$$b5
000136656 7001_ $$aYokota, Osamu$$b6
000136656 7001_ $$aIshihara, Kenji$$b7
000136656 7001_ $$aAng, Lee-Cyn$$b8
000136656 7001_ $$aBilbao, Juan M$$b9
000136656 7001_ $$0P:(DE-2719)9000939$$aMackenzie, Ian R.A.$$b10$$udzne
000136656 77318 $$2Crossref$$3journal-article$$a10.1007/s00401-012-1020-6$$b : Springer Science and Business Media LLC, 2012-07-28$$n5$$p705-716$$tActa Neuropathologica$$v124$$x0001-6322$$y2012
000136656 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-012-1020-6$$gVol. 124, no. 5, p. 705 - 716$$n5$$p705-716$$q124:5<705 - 716$$tActa neuropathologica$$v124$$x0001-6322$$y2012
000136656 8564_ $$uhttps://pub.dzne.de/record/136656/files/DZNE-2020-02978_Restricted.pdf
000136656 8564_ $$uhttps://pub.dzne.de/record/136656/files/DZNE-2020-02978_Restricted.pdf?subformat=pdfa$$xpdfa
000136656 909CO $$ooai:pub.dzne.de:136656$$pVDB
000136656 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810592$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000136656 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2810632$$aExternal Institute$$b1$$kExtern
000136656 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9000168$$aExternal Institute$$b3$$kExtern
000136656 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9000939$$aExternal Institute$$b10$$kExtern
000136656 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000136656 9132_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000136656 9141_ $$y2012
000136656 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000136656 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bACTA NEUROPATHOL : 2017
000136656 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000136656 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000136656 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000136656 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000136656 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000136656 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000136656 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000136656 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000136656 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000136656 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000136656 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000136656 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bACTA NEUROPATHOL : 2017
000136656 9201_ $$0I:(DE-2719)1210003$$kAG Neumann$$lMolecular Neuropathology of Neurodegenerative Diseases$$x0
000136656 980__ $$ajournal
000136656 980__ $$aVDB
000136656 980__ $$aI:(DE-2719)1210003
000136656 980__ $$aUNRESTRICTED
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M011446200$$o10.1074/jbc.M011446200
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0014-4827(03)00221-0$$o10.1016/S0014-4827(03)00221-0
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/jnnp.2009.194399$$o10.1136/jnnp.2009.194399
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-011-0863-6$$o10.1007/s00401-011-0863-6
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1365-2990.2012.01274.x$$o10.1111/j.1365-2990.2012.01274.x
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neures.2009.10.004$$o10.1016/j.neures.2009.10.004
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/emboj.2010.143$$o10.1038/emboj.2010.143
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1074/jbc.M111.273912$$o10.1074/jbc.M111.273912
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archneurol.2009.329$$o10.1001/archneurol.2009.329
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archneurol.2010.52$$o10.1001/archneurol.2010.52
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.22246$$o10.1002/ana.22246
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.yexcr.2008.12.008$$o10.1016/j.yexcr.2008.12.008
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkq1162$$o10.1093/nar/gkq1162
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1155/2011/837474$$o10.1155/2011/837474
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1166066$$o10.1126/science.1166066
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awr160$$o10.1093/brain/awr160
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bfgp/ell015$$o10.1093/bfgp/ell015
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2006.05.049$$o10.1016/j.cell.2006.05.049
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-009-0612-2$$o10.1007/s00401-009-0612-2
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S1474-4422(10)70195-2$$o10.1016/S1474-4422(10)70195-2
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-010-0764-0$$o10.1007/s00401-010-0764-0
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-011-0845-8$$o10.1007/s00401-011-0845-8
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-011-0838-7$$o10.1007/s00401-011-0838-7
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-009-0598-9$$o10.1007/s00401-009-0598-9
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awp214$$o10.1093/brain/awp214
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-009-0581-5$$o10.1007/s00401-009-0581-5
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awr201$$o10.1093/brain/awr201
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s12031-011-9549-8$$o10.1007/s12031-011-9549-8
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/mus.21665$$o10.1002/mus.21665
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1021/ac026283q$$o10.1021/ac026283q
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/jnnp.2010.214437$$o10.1136/jnnp.2010.214437
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-011-0816-0$$o10.1007/s00401-011-0816-0
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pbio.0060137$$o10.1371/journal.pbio.0060137
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/jmcb/mjp025$$o10.1093/jmcb/mjp025
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/hmg/ddr448$$o10.1093/hmg/ddr448
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-010-0698-6$$o10.1007/s00401-010-0698-6
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.1165942$$o10.1126/science.1165942
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1750-3639.2009.00337.x$$o10.1111/j.1750-3639.2009.00337.x
000136656 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jmb.2006.08.018$$o10.1016/j.jmb.2006.08.018
000136656 999C5 $$2Crossref$$oH Zinszner 1997$$y1997