Fig. 8.

A model for the TRC40-mediated delivery of short secretory proteins to the Sec61 translocon via WRB. Short secretory proteins are bound by TRC40 and targeted to the WRB receptor complex at the ER membrane. After release, the protein is transferred directly, or via unidentified components (dashed line), to the Sec61 complex, which is responsible for the translocation of the protein into the ER lumen. At least one alternative pathway exists that is independent of TRC40 and WRB but also appears to deliver precursors to the Sec61 translocon. We note that post-translational transport of ppcecA into the ER of semi-permeabilised cells is inhibited by siRNA-mediated depletion of Sec61 complex, Sec62 and Sec63 (Lang et al., 2012). In the absence of TRC40 (i.e. after immunodepletion), proteins use the alternative pathway(s). However, when TRC40 is present, WRBcc has a dominant-negative effect because proteins have committed to the TRC40-dependent route.