9.B.229. The Transferrin Receptor, CD71, (TFR) Family
The yeast manganese transporter, Smf1, is subject to two levels of regulation: heavy metal-induced sequestration in the cell and ubiquitination and degradation in the vacuole. Degradation requires Bsd2, a membrane protein with a PPxY motif that recruits the ubiquitin ligase Rsp5, and which plays a role in the quality control of membrane proteins that expose hydrophilic residues to the lipid bilayer. Stimpson et al. 2006 showed that degradation of Smf1 requires in addition one of a pair of related yeast proteins, Tre1 and Tre2, that also contain PPxY motifs. Tre1 can partially inhibit manganese uptake without Bsd2, but Bsd2 is required to induce Smf1 degradation. It has a relatively hydrophilic transmembrane domain and binds to Bsd2. Possibly, the Tre proteins specifically link Smf1 to the Bsd2-dependent quality control system. Their luminal domains are related to the transferrin receptor, but these are dispensable for Smf1 regulation (Stimpson et al. 2006).