Fig. 7: Effects of neurodegenerative proteins on PQBP5 and nucleolus decomposition.

a Immunohistochemistry of PQBP5 together with normal or mutant polyglutamine disease proteins. PQBP5 was sequestered to the inclusion bodies formed by mutant Htt in the striatal neurons of mutant Htt-KI mice (upper left panels) and in the inclusion bodies formed by mutant Atxn1 in the cortical neurons of mutant Atxn1-KI mice (upper middle panels). In some Purkinje cells of mutant Atxn1-KI mice, PQBP5 was sequestered to cytoplasmic inclusions (upper right panels). In all cases, fibrillarin and nucleolin lost their nucleolar assembly activity. Fibrillarin disappeared from the nucleoli, and nucleolin was dispersed in the nucleus. The right graphs in the left and middle columns show quantification of PQBP5-sequestered cells (upper graphs), cells lacking nucleolar fibrillarin (middle graphs), and cells lacking nucleolar nucleolin (lower graphs). The box plot shows median, 25–75th percentile, and whiskers representing data outside the 25–75th percentile range. Two-sided Student’s t-test was used for statistical examination. P-values are as follows. % PQBP5-sequestered cells: 0.0017, % fibrillarin-absent cells: 0.0053, % nucleolin-absent cells: 0.0003 in striatal neurons of Htt-KI mice at 78 weeks. % PQBP5-sequestered cells: 0.0018, % fibrillarin-absent cells: 0.0095, % nucleolin-absent cells: 0.0026 in cerebral cortex neurons of Atxn1-KI mice at 32 weeks. % PQBP5-sequestered cells: 0.0011, % fibrillarin-absent cells: 0.0002, % nucleolin-absent cells: 0.0006 in Purkinje cells of Atxn1-KI mice at 32 weeks. b EM analysis of nucleoli in Purkinje cells of mutant Atxn1-KI mice and in striatal neurons of mutant Htt-KI mice. The right bar graph shows the percentage of abnormal cells having morphological features of abnormal nucleoli (irregular shape, low electron density, loss of FC/DFC) in four mouse genotypes. Data are presented as mean values ± SEM. Tukey’s HSD test was used for multiple comparisons. P < 0.0001 in comparisons by GraphPad Prism.