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9.B.82 The  Endoplasmic Reticulum Retrieval Protein1 (Putative Heavy Metal Transporter) (Rer1) Family

Mutations in the gene encoding the 4 TMS (2 + 2) Rer1 protein in S. cerevisiae (of about 190 aas as are most of its homologues) can be complemented by human NRAMP1 (TC# 2.A.55.2.3), suggesting that it might be a heavy metal efflux pump (Techau et al., 2007). It has homologues in many fungi, animals, plants and other eukaryotes, almost all of about 190 aas. Single oraganisms can have multiple paralogues. Downregulation of Rer1 leads to increased surface localization of Pen2 (a component of the γ-secretase complex), whereas overproduction of Rer1 stabilizes unassembled Pen2. Rer1 is the first identified interaction partner of mammalian transmembrane-based retention/retrieval signals (Kaether et al. 2007).

RER1 localizes to the intermediate compartment and the cis-Golgi. From there it returns escaped proteins that are not supposed to leave the endoplasmic reticulum (ER) back to it. Unique about RER1 is its ability to recognize its ligands through binding motifs in its TMSs. Among its substrates are ER-resident proteins, as well as unassembled subunits of multimeric complexes that are retrieved back into the ER, thus guarding the full assembly of their respective complexes. The basic mechanisms for RER1-dependent retrieval are known in yeast, but several important cargoes of RER1 have been described in mammalian cells, and the in vivo role of RER1 is being unveiled by using mouse models. Annaert and Kaether 2020 give an overview of the cell biology of RER1 in different models, discuss its controversial role in the brain, and provide an outlook on future directions for RER1 research.

 

References associated with 9.B.82 family:

Annaert, W. and C. Kaether. (2020). Bring it back, bring it back, don''t take it away from me - the sorting receptor RER1. J Cell Sci 133:. 32873699
Kaether, C., J. Scheuermann, M. Fassler, S. Zilow, K. Shirotani, C. Valkova, B. Novak, S. Kacmar, H. Steiner, and C. Haass. (2007). Endoplasmic reticulum retention of the γ-secretase complex component Pen2 by Rer1. EMBO Rep 8: 743-748. 17668005
Techau, M.E., J. Valdez-Taubas, J.F. Popoff, R. Francis, M. Seaman, and J.M. Blackwell. (2007). Evolution of differences in transport function in slc11a family members. J. Biol. Chem. 282: 35646-35656. 17932044