KDEL receptor 1 (Kdelr1) dynamics and over-expression in therapeutic antibody producing CHO cells

摘要

Soluble ER chaperones (e.g. Protein disulfide isomerase, BiP and Calreticulin) are retrieved in the ER by their C-terminus KDEL motif. KDEL stands for the amino acids Lysine, Aspartic acid, Glutamic acid and Leucine [1]. KDEL receptors are seven transmembrane domain proteins found in the cis-Golgi and intermediate compartment, known to be responsible for the recycling of ER chaperones that carry folded proteins from ER to Golgi, back to ER after the delivery of the cargo [2]. Once these chaperones bind to KDEL receptor, the receptors can recapture them and return them back to the ER in COPI vesicles known as the retrograde pathway [3]. On the other hand, KDELR1 has also been reported to act as a traffic sensor that regulates the flux between ER and Golgi [4] by activating the anterograde pathway and activating the secretory machinery. The hypothesis of this study is to over-express KDELR1 in order to improve the retrieval of KDEL tagged ER chaperones and accordingly, increase the pool of chaperones inside the ER and improve the folding of the recombinant proteins. Alternatively, the effect of over-expression on protein quality in terms of aggregation and glycosylation will be further investigated.