Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates
| Autor: | Ronald Melki, Ron R. Kopito, Jane E. Lauckner, Pei-Hsien Ren, John E. Heuser, Ioulia Kachirskaia |
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| Přispěvatelé: | Department of Biology, Stanford University, Stanford University, Washington University in Saint Louis (WUSTL), Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Cytoplasm
[SDV]Life Sciences [q-bio] Cell Communication Protein aggregation Inclusion bodies MESH: Neurodegenerative Diseases Prion Diseases 0302 clinical medicine MESH: Trinucleotide Repeat Expansion Inclusion Bodies 0303 health sciences MESH: Peptides MESH: Proteasome Endopeptidase Complex Neurodegenerative Diseases Amyloidosis Endocytosis Cell biology Huntington Disease Aggresome MESH: Endocytosis Neurofibrils Amyloid Proteasome Endopeptidase Complex Cell signaling Neurofilament education MESH: Disease Transmission Infectious Biology Article Cell Line 03 medical and health sciences MESH: Cell Communication Disease Transmission Infectious Humans MESH: Amyloidosis 030304 developmental biology MESH: Amyloid MESH: Humans MESH: Cytoplasm MESH: Prion Diseases Cell Biology MESH: Inclusion Bodies MESH: Neurofibrils MESH: Huntington Disease MESH: Cell Line Cytosol Cell culture Peptides Trinucleotide Repeat Expansion 030217 neurology & neurosurgery |
| Zdroj: | Nature Cell Biology Nature Cell Biology, Nature Publishing Group, 2009, 11 (2), pp.219-25. ⟨10.1038/ncb1830⟩ |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb1830 |
| Popis: | International audience; Sequence-specific nucleated protein aggregation is closely linked to the pathogenesis of most neurodegenerative diseases and constitutes the molecular basis of prion formation. Here we report that fibrillar polyglutamine peptide aggregates can be internalized by mammalian cells in culture where they gain access to the cytosolic compartment and become co-sequestered in aggresomes together with components of the ubiquitin-proteasome system and cytoplasmic chaperones. Remarkably, these internalized fibrillar aggregates are able to selectively recruit soluble cytoplasmic proteins with which they share homologous but not heterologous amyloidogenic sequences, and to confer a heritable phenotype on cells expressing the homologous amyloidogenic protein from a chromosomal locus. |
| Databáze: | OpenAIRE |
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