Figure 1.

Aggregation of HTT_ex1 Proteins Can Involve a Conversion between Distinct Macroscopic Assemblies

(A) Domain organization of HTT_ex1 constructs in this study.

(B) Representative confocal maximum intensity projections of bright and dim 43QP-GFP assemblies. Scale bar, 10 μm.

(C and D) Time-lapse fluorescence microscopy of 43QP-GFP aggregation without (C), and with (D), a visible intermediate dim assembly. Orange arrows: bright assembly formation. Blue asterisk: coalescence of dim assemblies. Scale bar, 10 μm.

(E) Quantification of aggregation events occurring without (orange) and with (orange/blue) visible intermediate dim assemblies. n > 92 aggregation events per construct from three independent experiments. p = 0.0003, chi-square.

(F) FRAP experiment showing high HTT_ex1 mobility in dim assemblies but not in bright assemblies. Scale bar, 3 μm.

(G) Averaged FRAP recovery curves. Shaded areas represent 95% confidence interval (CI). Dim assemblies estimated mobile fraction = 84%, 95% CI: 83%–85%, n = 20; bright assemblies estimated mobile fraction = 10%, 95% CI: 10%–11%, n = 20. See also Table S1.

(H) EM projection image of a 43QP-GFP bright assembly (orange dashes). Higher-magnification image (inset) shows a network of fibrillar structures.

(I) 43QP-GFP bright assembly (orange) and dim assemblies (blue). Higher-magnification image (inset) shows fibrillar structures emanating from the dim assemblies. Low-magnification scale bar, 5 μm; high-magnification scale bar, 500 nm.