Fig. 2: Cryo-ET imaging of α-Syn aggregates seeded by MSA patient brain material in neurons.
From: In situ architecture of neuronal α-Synuclein inclusions
a A tomographic slice (thickness 1.4 nm) of an inclusion seeded by MSA patient brain material in a neuron expressing GFP-α-Syn. Auto; autophagosome, ER; endoplasmic reticulum, Lyso; lysosome, Mito; mitochondrion, MVB; multivesicular body, Ves; vesicles. Fibrils are marked by red arrowheads. Scale bar: 350 nm. b 3D rendering of the tomogram depicted in a showing α-Syn fibrils (red), autophagosomes (cyan), ER (yellow), a lysosome (gray), mitochondria (green), multivesicular bodies (orange), and various vesicles (purple). c Magnified view of a fibril with GFP-like densities (green arrowheads) decorating the fibril core. Scale bar: 30 nm. d Histogram of fibril length. n = 1592 (GFP-α-Syn + PFFs), 220 (endogenous α-Syn + PFFs), and 721 (GFP-α-Syn + MSA) fibrils analyzed over three biologically independent experiments for all conditions. e Box plots of cytosolic fibril density within inclusions, defined as the fraction of cytosolic volume occupied by fibrils. The horizontal lines of each box represent 75% (top), 50% (middle), and 25% (bottom) of the values, and a black square the average value. Whiskers represent 1.5× standard deviation and black diamonds the individual data points. n = 6 (GFP-α-Syn + PFFs), 4 (endogenous α-Syn + PFFs), and 5 (GFP-α-Syn + MSA) tomograms analyzed over three biologically independent experiments for all conditions; n.s., ** and *** indicate respectively p = 0.4, p = 0.0010, and p = 4 × 10−4 by one-way ANOVA. The number of fibrils, tomograms, and biologically independent cryo-ET experiments is listed in Supplementary Table 1. Representative images are shown in a–c. Source data for d and e are provided as a Source data file.
