The Arabidopsis Homolog of the Mammalian OS-9 Protein Plays a Key Role in the Endoplasmic Reticulum-Associated Degradation of Misfolded Receptor-Like Kinases

The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog （AtOS9） of an ER luminal lectin Yos9 （OS-9 in mammals） that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-Iocalized glyco- protein that is co-expressed with many known/predicted ER chaperones. AT-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid （BR） receptor bril-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bril-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-rnutagenized bril suppressor 6 （ebs6-1）. Moreover, we showed that atos9-t also inhibits the ERAD of bril-5, another ER-retained BR receptor, and a misfolded EFR, a BRIl-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian SellL known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.