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We show here that autophagic degradation is inhibited in cells depleted of ESCRT subunits and in cells expressing CHMP2B mutants, leading to accumulation of protein aggregates containing ubiquitinated proteins, p62 and Alfy. Moreover, we find that functional MVBs are required for clearance of TDP-43 (identified as the major ubiquitinated protein in ALS and frontotemporal lobar degeneration with ubiquitin deposits), and of expanded polyglutamine aggregates associated with Huntington's disease. Together, our data indicate that efficient autophagic degradation requires functional MVBs and provide a possible explanation to the observed neurodegenerative phenotype seen in patients with CHMP2B mutations.<\/jats:p>","DOI":"10.1083\/jcb.200702115","type":"journal-article","created":{"date-parts":[[2007,11,5]],"date-time":"2007-11-05T16:23:35Z","timestamp":1194279815000},"page":"485-500","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":583,"title":["Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease"],"prefix":"10.1083","volume":"179","author":[{"given":"Maria","family":"Filimonenko","sequence":"first","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Stuffers","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Raiborg","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"2Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Maler\u00f8d","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"3Department of Neurodegenerative Disease"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Isaacs","sequence":"additional","affiliation":[{"name":"4MRC Prion Unit, Institute of Neurology, University College London, London WC1N 3BG, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Brech","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Stenmark","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Simonsen","sequence":"additional","affiliation":[{"name":"1Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,11,5]]},"reference":[{"key":"2023072202101779900_BIB1","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1073\/pnas.0700036104","volume":"104","year":"2007","journal-title":"Proc. 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