Reply to Honoré: Masking of Signal Sequences in CREC Proteins by cDNA Subcloning in Epitope Vectors

This is a response to a letter by Honoré (1)

We appreciate that Dr. Honoré commented on our work. As Dr. Honoré pointed out, C-terminal masking of CREC proteins RCN1 and calumenin, but not Cab45, by V5-tag might influence final subcellular localization of the proteins by affecting the endoplasmic reticulum (ER) retrieval system. However, our finding in this study is that the Pro⁺² functions as an ER export signal. In this regard, it is important to note that the KDEL and KDEL-like motifs function to be retrieved to the ER by KDEL receptor after the proteins are exported from the ER. In addition to the ER, post-ER sites in the secretory pathway such as the Golgi, cell surface, and extracellular space, can be indeed localization sites of several proteins with KDEL or KDEL-like motif, including BiP (a representative ER chaperone), RCN1, and calumenin proteins (2–5). The balance of “export and retrieval” and final subcellular localization might be influenced by C-terminal masking, but the notion does not conflict the importance of our finding of Pro⁺² as “an ER export signal.”