Wu Yachen,Zheng Wenzhong,Xu Guofeng,Zhu Lijun,Li Zhiqiang,Chen Jincao,Wang Lianrong,Chen Shi
Sterol regulatory element binding transcription factors (SREBPs) play a crucial role in lipid homeostasis. They are processed and transported to the nucleus via COPII, where they induce the expression of lipogenic genes. COPII maintains the homeostasis of organelles and plays an essential role in the protein secretion pathways in eukaryotes. The formation of COPII begins at endoplasmic reticulum exit sites (ERES), and is regulated by SEC16A, which provides a platform for the assembly of COPII. However, there have been few studies on the changes in SEC16A protein levels. The repetitive expansion of the hexanucleotide sequence GGGGCC within the chromosome 9 open reading frame 72 (C9orf72) gene is a prevalent factor in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we found that the absence of C9orf72 leads to a decrease in SEC16A protein levels, resulting in reduced localization of the guanine nucleotide exchange factor SEC12 at the ERES. Consequently, the small GTP binding protein SAR1 is unable to bind the endoplasmic reticulum normally, impairing the assembly of COPII. Ultimately, the disruption of SREBPs transport decreases de novo lipogenesis. These results suggest that C9orf72 acts as a novel role in regulating lipid homeostasis and may serve as a potential therapeutic target for obesity.
The eukaryotic chaperonin containing T-complex polypeptide-1 (CCT/TRiC) complex, composed of eight distinct subunits (CCT1–CCT8), is essential for cytosolic protein folding; however, its function in plants remains largely unexplored. Moreover, a direct link between CCT and coat protein complex II (COPII) vesicle trafficking—a key step in the early secretory pathway—has not been established in any eukaryotic system. Here, leveraging plant genetics, we investigated the functional relationship between CCT8 and COPII-mediated trafficking in the Arabidopsis root apex. The point mutant cct8-1 exhibited a short-root phenotype resulting from impaired cell division in the root meristem, which was accompanied by disrupted auxin homeostasis. This defect stemmed from a marked reduction in the abundance of multiple PIN-FORMED (PIN) auxin efflux carriers at the plasma membrane, without affecting their polar localization. Mechanistically, CCT8 directly interacted with SEC31B, a core component of the COPII coat. Accordingly, the sec31b-3 mutant phenocopied cct8-1 in root growth, auxin response, and PIN accumulation defects. The CCT8 mutation reduced SEC31B abundance at both the transcriptional and protein levels and compromised ER-to-Golgi transport, thereby diminishing PIN delivery to the plasma membrane. Importantly, overexpression of SEC31B partially rescued the root growth defects and restored PIN2 levels in cct8-1 . Together, our findings uncover a previously unrecognized chaperonin-trafficking module in which CCT8 regulates SEC31B to modulate COPII-mediated delivery of PIN proteins, thus linking chaperonin function to auxin-dependent root development.
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