“…STX5 – a target-SNARE – is required for fusion of retrograde vesicles with the TGN, and knockdown of its expression is sufficient to trap ricin in the early endosome (Amessou et al, 2007; Dascher and Balch, 1996; Suga et al, 2005; Norlin et al, 2016; Bennett et al, 1993). Most SNAREs like STX5 are tail-anchored (TA) proteins – a class of membrane proteins with a single, C-terminal transmembrane domain (TMD) that are post-translationally targeted to the ER for insertion by the transmembrane domain recognition complex (TRC) pathway (Hegde and Keenan, 2011; Denic, 2012; Cho et al, 2018). Notably, our previous genome-wide CRISPR/Cas9 deletions screens have identified STX5 and its ER targeting factor, ASNA1 (also known as TRC40) among the top hits that confer resistance to ricin (Morgens et al, 2017).…”