A di-arginine motif contributes to the ER-localization of the type I transmembrane ER oxidoreductase TMX4

Doris Roth , Emily Lynes , Jan Riemer , Henning G. Hansen , Nils Althaus , Thomas Simmen , Lars Ellgaard (1)

1 Department of Biology [Copenhagen]

The thiol-disulfide oxidoreductases of the protein disulfide isomerase (PDI) family assist disulfide-bond formation in the endoplasmic reticulum (ER). Here, we show that the previously uncharacterized PDI-family member TMX4 is an N-glycosylated type I membrane protein that localizes to the ER. We also demonstrate that TMX4 contains a single ER-lumenal thioredoxin-like domain, which – in contrast to similar domains in other PDIs – is mainly oxidized in living cells. The TMX4 transcript displays a wide tissue distribution, and is strongly expressed in melanoma cells. Unlike many type I membrane proteins, TMX4 lacks a typical C-terminal di-lysine retrieval signal. Instead, the cytoplasmic tail harbors a conserved di-arginine motif of the RXR type. We show that mutation of the RQR sequence in TMX4 to KQK interferes with ER localization of the protein. Moreover, whereas the cytoplasmic region of TMX4 confers ER localization to a reporter protein, the KQK mutant of the same protein redistributes to the cell surface. Overall, features not commonly found in other PDIs characterize TMX4 and suggest unique functional properties of the protein.

Mots clés: Life Sciences

Doris Roth, Emily Lynes, Jan Riemer, Henning G. Hansen, Nils Althaus, et al.. A di-arginine motif contributes to the ER-localization of the type I transmembrane ER oxidoreductase TMX4. Biochemical Journal, 2009, 425 (1), pp.195-205. ⟨10.1042/BJ20091064⟩. ⟨hal-00479227⟩