Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
EMBO Rep. 2022 Jul 5;23(7):e54163. doi: 10.15252/embr.202154163. Epub 2022 May 19.
N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.
N-糖链是 70%以上穿越分泌途径的蛋白质所携带的分子多样性糖,参与蛋白质折叠、稳定性和定位。参与 N-糖基化的基因发生突变会导致先天性糖基化紊乱,这些紊乱通常与智力障碍有关。在这里,我们表明,结构不同的 N-糖链调节参与秀丽隐杆线虫体感树突模式形成的细胞外蛋白质复合物。具体来说,aman-2/高尔基 α-甘露糖苷酶 II 是特定 N-糖生物合成中的一种保守关键酶,它调节 Menorin 粘附复合物的活性,而不会明显影响其成分的蛋白质稳定性和定位。AMAN-2 以细胞自主的方式起作用,使神经元跨膜受体 DMA-1/LRR-TM 被正确的高甘露糖/杂合/低甘露糖 N-糖链修饰。此外,特定 N-糖基化位点上的不同类型的 N-糖链调节 DMA-1/LRR-TM 受体功能,该受体与其他三个细胞外蛋白一起形成 Menorin 粘附复合物。总之,特定的 N-糖链结构通过协调细胞外粘附复合物的活性来调节树突的模式形成,这表明 N-糖链的分子多样性可以为神经系统的发育特异性做出贡献。