Fig. 2: Pathological TDP-43 aggregates contain components of the nucleocytoplasmic transport machinery.
From: TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD
a, Mass spectrometry analysis of proximity-biotinylated proteins associated with BirA*-TDP-43 and BirA*-TDP-CTF. The 202 proteins present in both datasets accounted for 80% of the TDP-43- and 52% of the TDP-CTF-associated proteome. b, Mapping the number of identified peptide spectra matches for the interacting protein of TDP-43 and TDP-CTF (circle). The relative abundance ratio (log2-fold change) between TDP-CTF- and TDP-43-associated proteome is shown by circle size and color. Positive values indicate predominant association with TDP-CTF (blue), negative values with TDP-43 (red). The dotted line indicates the cut-off threshold. c, Gene ontology (GO) analysis of proteins preferentially associated with TDP-43 or TDP-CTF. P values indicate the probability of seeing that number of proteins annotated to a particular GO term, given the proportion of proteins in the total mouse proteome that are annotated to that GO term. d, Network analysis of the TDP-CTF versus TDP-43 proteome in the nucleocytoplasmic transport pathway by GeneMANIA. Gray circles represent unidentified proteins. Colored circles represent the identified proteins and their peptide spectra matches in the TDP-CTF- and TDP-43-associated proteomes (blue and red, respectively). Circle sizes reflect log2-fold change between TDP-CTF and TDP-43. e, Summary diagram of the TDP-CTF interaction screen with 37 proteins involved in nucleocytoplasmic transport (left) and representative images of the coaggregation (arrows) of GFP-tagged proteins with mCherry-TDP-CTF in N2a cells (right). Images for all tested components of the nucleocytoplasmic transport machinery are shown in Supplementary Figs. 4 and 5. Each experiment was repeated independently two to four times. Scale bar: 10 μm.
