Science Advances, 20 May, 2026, DOI：https://doi.org/10.1126/sciadv.aee4450
COST1 stimulates RHD3 GTPase activity to maintain ER morphology and plant growth in Arabidopsis
Jiaojiao Wang, Jian Jiang, Jie Ren, Yunxi Zhao, Yu Zhang, Deyu Feng, Yanjie Li, Qian Zhang, Yue Niu, Xin Zhang, Kang Xu, Jiaqi Sun, Pengwei Wang, Huanquan Zheng, Diane C. Bassham, Chengyuan Wang, Junjie Hu, and Yan Bao
Abstract
The endoplasmic reticulum (ER) is essential for cellular homeostasis, yet plant-specific mechanisms regulating its structure remain poorly understood. Here, we uncover a functional partnership between the Arabidopsis dynamin-like GTPase RHD3 and the plant-specific DUF641 protein COST1 in maintaining ER morphology and plant growth. COST1 was previously isolated as a negative regulator of autophagy in the drought response. In this study, by using IP-MS, we identified COST1 as an ER-associated protein that interacts directly with RHD3, a key regulator of ER membrane fusion. COST1, despite lacking transmembrane domains, tightly associates with the ER membrane via RHD3, which recruits COST1 to ER three-way junctions. In addition, recruiting of COST1 to the ER can improve the dimerization of RHD3 and its protein stability. Biochemical assays revealed that COST1 promotes the GTP hydrolysis activity of RHD3 by ~20% and significantly stimulates its membrane fusion capacity. Structural modeling predicts a heterotetrameric complex entangled with each protein’s multiple helix bundles, where COST1’s carboxyl-terminal domain aligns with RHD3’s GTPase region, suggesting a mechanism for GTP hydrolysis regulation. Genetic analyses demonstrated that cost1 rhd3 double mutants exhibit exacerbated ER fragmentation and stunted growth compared with single mutants, underscoring their synergistic roles. Transcriptomic profiling linked these phenotypes to disordered stress responding and growth pathways. Our findings reveal a plant-specific regulatory module in which COST1 partners with RHD3 to govern ER architecture, bridging membrane dynamics with growth and stress adaptation, providing insights into ER maintenance mechanisms with plant innovations and the potential applications in improving crop resilience.
文章链接：https://www.science.org/doi/10.1126/sciadv.aee4450
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