Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.

The visual comparison of the cellular distribution of GFP-Atx3 15Q or 70Q with their respective K0 variants pointed to a slightly increased nuclear localization of the latter, whereas 70Q constructs carrying single lysine residues at positions K8 or K85 did not show a clear trend toward ataxin-3 compartmentalization ( Figure 2A ).

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Moreover, lysine-free ataxin-3 (K0) showed significantly lower protein levels for its 15Q form as well as a strong trend toward reduction for Atx3 70Q when compared to the unmutated counterparts.

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Lysine-free ataxin-3 had a strongly reduced protein level in its non-pathogenic form (15Q K0), whereas pathologically expanded ataxin-3 without lysine residues (70Q K0) presented a trend toward reduced protein levels (in comparison to Atx3 15Q and 70Q, respectively), which translated into a highly significant lower aggregate load.

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