Fig 1: VCP cofactors differentially regulate tau seeding.VCP cofactors were either knocked out via CRISPR/Cas9 (A-E) or knocked down via siRNA (F-I) in v2L biosensors prior to exposure to increasing amounts of tau fibrils. (A) Knockout of FAF2 increased tau seeding whereas knockout of (B) ATXN3, (C) NSFL1C, and (D) UBE4B reduced tau seeding. P values: FAF2 (*** =0.0001, **** < 0.0001); ATXN3 (**** < 0.0001); NSFL1C (*** =0.0002); UBE4B (**** < 0.0001). (E) Cofactor KO did not affect tau uptake.P values: ns = 0.98, 0.998, 0.995, 0.99, in order of bars on the graph. (F) Knockdown of NGLY1, (G) NPLOC4, and (H) OTUB1, decreased tau seeding. P values: NGLY1(**** < 0.0001); NPLOC4 (**** < 0.0001); OTUB1 (*** =0.0004, **** < 0.0001, *** =0.0001). (I) KD did not affect tau uptake. P values: ns = 0.98, 0.19, 0.39, in order of bars on the graph. Graphs are representative of n= 3 separate experiments. Error bars represent S.D. for (A-D; F-H), S.E.M. for (E,I). One-Way ANOVA (Šídák method) with a 95% confidence interval.