Extended Data Fig. 6: Proteomic profiling of postnuclear supernatant (PNS) and Endo-IP from TMEM230 mutant iNeurons.
From: EndoMAP.v1 charts the structural landscape of human early endosome complexes
a,b, Volcano plots of PNS proteomic analysis from TMEM230-/- (panel a) and TMEM230X121W (panel b) iNeurons compared to WT (day 21) (n = 3 biologically independent replicates). c, Violin plot showing the fold-change enrichment (log2) of proteins from individual organelle compartments in PNS from TMEM230-/- and TMEM230X121W iNeurons compared to WT (day 21). d, SynGO location enrichment analysis of proteins significantly regulated in PNS from TMEM230X121W iNeurons (Supplementary Table 4). The indicated categories were significantly enriched (−log10q-value). e,f, Volcano plots of Endo-IP proteomic analysis from TMEM230-/- (panel e) and TMEM230X121W (panel f) iNeurons compared to WT (day 21) (n = 3 biologically independent replicates). g, Heatmap showing the abundance fold-changes (log2) for all significantly regulated proteins in Endo-IPs from TMEM230-/- or TMEM230X121W iNeurons (21 day) compared to WT. Synaptic proteins annotated in SynGO (see METHODS) are indicated in bold. Asterisks indicate significantly regulated proteins (q-value < 0.05 and fold-change > 1.5). Abundance fold-changes in PNS are also indicated, except for proteins not detected (nd). h, Heatmap for the abundance fold-changes (log2FC) of selected proteins in PNS and Endo-IPs from TMEM230-/- or TMEM230X121W iNeurons (21 day) compared to WT. Asterisks indicate significantly regulated proteins (q-value < 0.05 and fold-change > 1.5) and nd for proteins not detected. i, Summary of pairwise AF-M predictions harboring candidate disease variants within 2 amino acids of the interface for endosomal and non-endosomal proteins. j, Candidate disease variants at the interaction interface of pairwise protein AF-M predictions. Predicted aligned error plots (left), predicted structures with ipTMs (center left, interprotein DSSO cross-links indicated by red lines) and close-up view of disease variant residues (yellow) at the interaction interface (center right, and right; dotted lines indicate predicted hydrogen bonds).
