# The Hrd1-Mediated ERAD Pathway in Plants: Conserved Principles and Plant-Specific Innovations

**Authors:** Jiarui Wu, Peiqi Huang, Jianming Li

PMC · DOI: 10.3390/ijms27041801 · International Journal of Molecular Sciences · 2026-02-13

## TL;DR

This paper explores how plants use the Hrd1-mediated ERAD pathway to manage protein quality control, revealing both conserved mechanisms and plant-specific adaptations.

## Contribution

The paper identifies plant-specific innovations in the Hrd1 ERAD pathway and its integration with hormone signaling and stress responses.

## Key findings

- Plants retain the core Hrd1 ERAD architecture but include additional regulatory elements.
- The plant Hrd1 complex integrates ERQC with hormone signaling, stress adaptation, and immune responses.
- Genetic and biochemical analyses reveal conserved and novel components of the plant ERAD pathway.

## Abstract

Endoplasmic reticulum-mediated protein quality control (ERQC) safeguards secretory pathway proteostasis by recognizing, retaining, repairing, and removing misfolded proteins, and is therefore essential for plant growth, development, and stress tolerance. This system relies on ER-associated degradation (ERAD), in which irreparably misfolded proteins are first recognized in the ER, then exported across the ER membrane to the cytosol, where they are ubiquitinated by ER membrane-anchored ubiquitin ligases, and subsequently degraded by the cytosolic proteasome. Studies in yeast and mammals have defined several conserved ERAD branches, including a multiprotein ERAD complex centered on the polytopic ER membrane E3 ligase HMG-CoA reductase degradation protein 1 (Hrd1), which integrates substrate recognition, membrane retrotranslocation, ubiquitin conjugation, and cytosolic extraction. Recent advances in Arabidopsis show that plants retain the core Hrd1 ERAD architecture while incorporating additional regulatory elements that adapt this machinery to plant-specific physiological demands. Genetic and biochemical analyses of misfolded receptor kinases and engineered substrates have uncovered conserved and plant-specific components of the plant Hrd1 complex, revealing how the plant ERAD pathway integrates ERQC with hormone signaling, stress adaptation, immune responses, and growth regulation. This review synthesizes recent advances in plant ERAD research and highlights key conceptual and mechanistic questions that remain to be resolved.

## Linked entities

- **Genes:** SYVN1 (synoviolin 1) [NCBI Gene 84447]
- **Proteins:** SYVN1 (synoviolin 1)
- **Species:** Arabidopsis (taxon 3701)

## Full-text entities

- **Genes:** CUE1 (Cue1p) [NCBI Gene 855306] {aka KIS4}, AIM24 (Aim24p) [NCBI Gene 853543] {aka FMP26}, OS9 (ER lectin-like protein) [NCBI Gene 833459] {aka AtOS9, F7N22.4, F7N22_4}, UBC27 (ubiquitin-conjugating enzyme 27) [NCBI Gene 835159] {aka K3K7.1, K3K7_1, ubiquitin-conjugating enzyme 27}, FAF1 (Faf1p) [NCBI Gene 854793], NPL4 (nuclear protein localization protein 4) [NCBI Gene 852468] {aka HRD4}, UBC32 (ubiquitin-conjugating enzyme 32) [NCBI Gene 820956] {aka ubiquitin-conjugating enzyme 32}, UFD1 (polyubiquitin-binding protein UFD1) [NCBI Gene 852939], EBS1 (Ebs1p) [NCBI Gene 851787], OTU1 (ubiquitin-specific protease OTU1) [NCBI Gene 850500], UBC6 (E2 ubiquitin-conjugating protein UBC6) [NCBI Gene 856837] {aka DOA2}, CDC48 (AAA family ATPase CDC48) [NCBI Gene 851431], UBC1 (ubiquitin carrier protein 1) [NCBI Gene 838002] {aka ATUBC1, F14L17.17, F14L17_17, UBIQUITIN CARRIER PROTEIN 1, UBIQUITIN CONJUGATING ENZYME 1, ubiquitin carrier protein 1}, UBC6 (ubiquitin-conjugating enzyme 6) [NCBI Gene 819211] {aka T3F17.32, ubiquitin-conjugating enzyme 6}, PTC6 (type 2C protein phosphatase PTC6) [NCBI Gene 850441] {aka AUP1, PPP2}, UBC1 (E2 ubiquitin-conjugating protein UBC1) [NCBI Gene 851757], UBX2 (Ubx2p) [NCBI Gene 854995] {aka SEL1}, UBI4 (ubiquitin) [NCBI Gene 850620] {aka SCD2, UB14}, USA1 (Usa1p) [NCBI Gene 854979], AT5G43710 (Glycosyl hydrolase family 47 protein) [NCBI Gene 834391] {aka MNS4, MQD19.4, MQD19_4, mannosidase 4}, HRD1 (E3 ubiquitin-protein ligase HRD1) [NCBI Gene 854149] {aka DER3}, UBC7 (ubiquitin-conjugating enzyme E2) [NCBI Gene 836048] {aka ARABIDOPSIS THALIANA UBIQUITIN CARRIER PROTEIN 7, ATUBC7, MNC17.22, MNC17_22, ubiquitin carrier protein 7}, DER1 (derlin) [NCBI Gene 852500], RNR4 (ribonucleotide-diphosphate reductase subunit RNR4) [NCBI Gene 853091] {aka CRT3, PSO3}, EBS5 (HCP-like superfamily protein) [NCBI Gene 838406] {aka EMS-mutagenized bri1 suppressor 5, HRD3A, T10O22.22, T10O22_22}, SSM4 (E3 ubiquitin-protein ligase SSM4) [NCBI Gene 854781] {aka DOA10, KIS3}, UBC33 (ubiquitin-conjugating enzyme 33) [NCBI Gene 835111] {aka MXI22.15, MXI22_15, ubiquitin-conjugating enzyme 33}, HRD3 (ubiquitin ligase complex subunit HRD3) [NCBI Gene 850904], UBC7 (E2 ubiquitin-conjugating protein UBC7) [NCBI Gene 855036] {aka DER2, QRI8}, YOS9 (Yos9p) [NCBI Gene 851627], PNG1 (peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase) [NCBI Gene 856009], AT1G27520 (Glycosyl hydrolase family 47 protein) [NCBI Gene 839643] {aka MNS5, T17H3.2, T17H3_2, mannosidase 5}, CUE1 (Glucose-6-phosphate/phosphate translocator-like protein) [NCBI Gene 833308] {aka ARABIDOPSIS THALIANA PHOSPHATE/PHOSPHOENOLPYRUVATE TRANSLOCATOR, ARAPPT, CAB UNDEREXPRESSED 1, F19N2.40, F19N2_40, PHOSPHOENOLPYRUVATE/PHOSPHATE TRANSLOCATOR}, BRI1 (Leucine-rich receptor-like protein kinase family protein) [NCBI Gene 830095] {aka ATBRI1, BIN1, BR INSENSITIVE 1, BRASSINOSTEROID INSENSITIVE 1, CABBAGE 2, CBB2}, CNE1 (calnexin) [NCBI Gene 851241] {aka FUN48}, UBC34 (ubiquitin-conjugating enzyme 34) [NCBI Gene 838300] {aka F20D23.1, F20D23_1, ubiquitin-conjugating enzyme 34}
- **Diseases:** blast disease (MESH:D001753), infection (MESH:D007239), hypersensitivity (MESH:D004342), ERAD (MESH:D055959), dwarf (MESH:D004393), injury to (MESH:D014947), MLO (MESH:D060467), dwarfism (MESH:D004392)
- **Chemicals:** ERAD-L (-), selenium (MESH:D012643), selenate (MESH:D064586), sterol (MESH:D013261), lipid (MESH:D008055), Cytokinin (MESH:D003583), carbon dioxide (MESH:D002245), ATP (MESH:D000255), heavy metal (MESH:D019216), calcium (MESH:D002118), auxin (MESH:D007210), jasmonate (MESH:C011006), oxygen (MESH:D010100), salt (MESH:D012492), cutin (MESH:C000521), E2 (MESH:D004958), luminal (MESH:D010634), asparagine (MESH:D001216), brassinosteroid (MESH:D060406)
- **Species:** Medicago (medics, genus) [taxon 3877], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Solanum lycopersicum (tomato, species) [taxon 4081], Homo sapiens (human, species) [taxon 9606], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Ricinus communis (castor bean, species) [taxon 3988], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Mutations:** Ser662-Phe, Cys69-Tyr

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## References

144 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940902/full.md

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Source: https://tomesphere.com/paper/PMC12940902