Fig. 4

Filamentous tau stimulates conventional and unconventional protein secretion in PAs. (A-C) Representative Coomassie blue-stained gels show increased protein secretion in PAs treated with tau PFF (A), which was significantly inhibited in cells pretreated with the FAK inhibitor PF-562271 (PF271) (B), or the NFκb inhibitor PDTC (C). The arrows in (A) indicate significant protein bands only detected in tau PFF-treated condition medium. For each condition, conditioned medium (1 mL) was concentrated 10 times using Amicon Ultra 3 K centrifugal filters, and 20 μL concentrated medium was loaded. Shown are representative gels from three biological repeats. (D) Two independent mass spectrometry analyses of conditioned medium from tau PFF-treated PAs compared to PBS-treated ones (Rep., Replication). (E) The molecular weight distribution of proteins whose secretion was induced by at least 2-fold by tau PFF in PAs. (F) A scatter plot showing the Log Fold Change (x-axis) and the relative intensity (abundance) of tau PFF-induced secretory proteins. Red dots represent proteins bearing a signal sequence (SS). Blue dots highlight a few induced chemokines. (G) STRING network analysis of tau PFF-induced secretory proteins. FDR, false discovery rate. (H) Examples of the STRING networks of proteins of the indicated pathways. The node size indicates the relative abundance in CM from tau-PFF treated PAs. The color indicates LFC caused by tau PFF. (I) Tau PFF-induced protein secretion is partially regulated by a post-transcriptional mechanism. The green shaded genes (co-reg., co-regulated) show similar induction in protein secretion (Pro. Sec.) and mRNA expression