| Autor: |
Sahl SJ; Department of Chemistry, Stanford University , Stanford, CA, USA., Weiss LE, Duim WC, Frydman J, Moerner WE |
| Jazyk: |
angličtina |
| Zdroj: |
Scientific reports [Sci Rep] 2012; Vol. 2, pp. 895. Date of Electronic Publication: 2012 Nov 28. |
| DOI: |
10.1038/srep00895 |
| Abstrakt: |
The identities of toxic aggregate species in Huntington's disease pathogenesis remain ambiguous. While polyQ-expanded huntingtin (Htt) is known to accumulate in compact inclusion bodies inside neurons, this is widely thought to be a protective coping response that sequesters misfolded conformations or aggregated states of the mutated protein. To define the spatial distributions of fluorescently-labeled Htt-exon1 species in the cell model PC12m, we employed highly sensitive single-molecule super-resolution fluorescence imaging. In addition to inclusion bodies and the diffuse pool of monomers and oligomers, fibrillar aggregates -100 nm in diameter and up to -1-2 µm in length were observed for pathogenic polyQ tracts (46 and 97 repeats) after targeted photo-bleaching of the inclusion bodies. These short structures bear a striking resemblance to fibers described in vitro. Definition of the diverse Htt structures in cells will provide an avenue to link the impact of therapeutic agents to aggregate populations and morphologies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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