Two ubiquitin-associated ER proteins interact with COPT copper transporters and modulate their accumulation. Issue 4 (9th August 2021) - Li, Xifeng
Abstract: The endoplasmic reticulum (ER) contains an elaborate protein quality control network that promotes protein folding and prevents accumulation of misfolded proteins. Evolutionarily conserved UBIQUITIN-ASSOCIATED DOMAIN-CONTAINING PROTEIN 2 (UBAC2) is involved in ER-associated protein degradation in metazoans. We have previously reported that two close UBAC2 homologs from Arabidopsis ( Arabidopsis thaliana ) not only participate in selective autophagy of ER components but also interact with plant-specific PATHOGEN-ASSOCIATED MOLECULAR PATTERN (PAMP)-INDUCED COILED COIL (PICC) protein to increase the accumulation of POWDERY MILDEW-RESISTANT 4 callose synthase. Here, we report that UBAC2s also interacted with COPPER (Cu) TRANSPORTER 1 (COPT1) and plasma membrane-targeted members of the Cu transporter family. The ubac2 mutants were significantly reduced in both the accumulation of COPT proteins and Cu content, and also displayed increased sensitivity to a Cu chelator. Therefore, UBAC2s positively regulate the accumulation of COPT transporters, thereby increasing Cu uptake by plant cells. Unlike with POWDERY MILDEW RESISTANCE 4, however, the positive role of UBAC2s in the accumulation of COPT1 is not dependent on PICC or the UBA domain of UBAC2s. When COPT1 was overexpressed under the CaMV 35S promoter, the increased accumulation of COPT1 was strongly UBAC2-dependent, particularly when a signal peptide was added to the N-terminus of COPT1. Further analysis using inhibitors of protein synthesis and degradation strongly suggested that UBAC2s stabilize newly synthesized COPT proteins against degradation by the proteasome system. These results indicate that plant UBAC2s are multifunctional proteins that regulate the degradation and accumulation of specific ER-synthesized proteins. Abstract : Two endoplasmic reticulum-resident UBIQUITIN-ASSOCIATED DOMAIN-CONTAINING PROTEIN 2s play an important role in copper accumulation through interacting COPT copper transporters and modulating their accumulation.