Figure 1.

Proteomic profiling of sacsin KO cells

(A) Representative confocal images of control (WT) and sacsin KO SH-SY5Y neuroblastoma cells immunostained for the intermediate filament protein vimentin. Scale bars, 10 μm.

(B) Global proteomic profiling of sacsin KO SH-SY5Y cells. Significance cutoffs: p < 0.05 and log₂ fold change (f.c.) ±0.4, denoted by black outline.

(C) Functional analysis of altered phosphosites in sacsin KO cells. y axis is the functional score assigned by Ochoa et al. (2020), with higher scores reflecting increased effects on fitness. Dot color and size reflect log₂ f.c. Black outlines label phosphosites with p < 0.05 and log₂ f.c. ±0.4.

(D) Phylogenetic tree of the kinome in sacsin KO cells. Color indicates log₂ f.c. of kinase abundance, size indicates −log₁₀ p value. Underlined abbreviations refer to phylogenetically related kinase families.

(E) Protein map of tau isoform 2 (2N4R). Phosphosites identified in phosphoproteomic profiling are labeled above diagram. Tau kinases identified in the kinome profiling are listed below, indicating validated phosphosites. Colored circles correlate with log₂ f.c. of differentially expressed phosphosites or kinases.

(F–H) Western blot and quantification for BRSK2, and the BRSK2 target residue pTAU S262. n = 3, SEM, Student’s t test, ^∗∗∗p < 0.001.