Recently, Professor Li Kunpeng's group from the School of Life Sciences of Shandong University published a research article entitled “Membralin is required for maize development and defines a branch of the endoplasmic reticulum-associated degradation pathway in plants” in Proc Natl Acad Sci U S A. The study revealed that ZmNLD1 encodes an ER membrane-localized membrane protein and specifically interacts with RING domain-containing E3-ubiquitin ligases RNF185 and RNF5, forming a branch of the ERAD pathway essential for maize plant development, independent of the classical HRD1 and Doa10 ERAD complexes.

Endoplasmic reticulum (ER)-associated degradation (ERAD) machinery enforces protein homeostasis control by eliminating aberrant or unnecessary proteins during protein folding, which plays an important role in plant growth and development and environmental adaptation. Membralin is a conserved ER membrane protein that lacks well-defined domains and preferentially accumulates in the central nervous systems of mammals. Its dysfunction is closely associated with neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Membralin deficiency attenuates the degradation rate of ERAD substrates and thus promotes necrosis of motor neurons, leading to mortality in young mice (Mus musculus) soon after birth. Membralin partners with the E3 ubiquitin ligase Ring Finger Protein 185 (RNF185), forming a branch of the ERAD pathway essential for quality control of ER membrane proteins independent of the classical ERAD complexes in mammals. However, whether this branch functions in plants is unknown.

Here, we report the map-based cloning and characterization of Narrow Leaf and Dwarfism 1(NLD1), which encodes the ER membrane-localized protein membralin, and specifically interacts with maize homologs of RNF185 and related components. nld1 mutant shows defective leaf and root development due to reduced cell number. The defects of nld1 were largely restored by expressing membralin genes from Arabidopsis thaliana and mouse, highlighting the conserved roles of membralin proteins in animals and plants. The activation of bZIP60 mRNA splicing–related unfolded protein response (UPR) signalling and marker gene expression innld1, as well as DNA fragment, cell viability assays, RNA-seq analysis and abiotic stress indicate that membralin deficiency induces ER stress and cell death in maize, thereby affecting organogenesis.

We propose a model describing the indispensable role of membralin encoded by NLD1 in maize. As a component of an ERAD complex, membralin functions in ER homeostasis by targeting its substrates such as HMGR and misfolded membrane proteins. Membralin deficiency or functional impairment leads to persistent ER stress and the UPR, resulting in PCD. Thus, membralin functions in an essential branch of the ERAD pathway that was not previously recognized in plants.

Shandong University is the first authors' and unique corresponding authors' affiliation. Professor Li Kunpeng is the corresponding author. Liu Baiyu, a PhD candidate at the School of Life Sciences of Shandong University, Xu Changzheng, a professor at the School of Life Sciences of Southwest University, He Qiuxia, a researcher at Qilu University of Technology, and Zhang Ke, a graduate student, are co-first authors of this paper. This work was supported by grants from the National Natural Science Foundation of China and the Key R&D Program of Shandong Province, China.

Article Link：https://doi.org/10.1073/pnas.2406090121