A selective interaction between OS-9 and the carboxyl-terminal tail of meprin β

Abstract

OS-9, a protein previously uncharacterized, was shown to interact specifically with the intracellular region of the membrane proteinase meprin β found in brush border membranes of kidney and small intestine. We have shown previously that this cytoplasmic region is indispensable for the maturation of meprin β, which included an endoplasmic reticulum (ER)-to-Golgi translocation. We characterized OS-9 and found that it is associated with ER membranes and that it is exposed to the cytoplasm. Consistent with the kinetics of maturation of meprin β, OS-9 associates with meprin β only transiently, coinciding with ER-to-Golgi transport of meprin β. The OS-9-binding site in the cytoplasmic domain of meprin β overlaps the region essential for this transport. We characterized alternatively spliced forms of rat and mouse OS-9, and we found that only the nonspliced form of OS-9 binds to meprin β, implicating the spliced out segment in lthe binding, and suggesting the possible mechanism of the regulation of OS-9 function. Taken together, our results indicated that OS-9 may be involved in the ER-to-Golgi transport of meprin β. Ubiquitous expression of OS-9 raises the possibility that it may interact with other membrane proteins that possess the cytoplasmic moiety homologous to that of meprin β during their ER-to-Golgi transition.