Specific N ‐glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning

Abstract

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. image 70% of proteins transiting the secretory pathway bear structurally diverse N‐ glycans, which have been suggested to function in protein folding and trafficking. This study shows that specific N‐ glycans regulate the function of a multipartite adhesion complex during patterning of dendrites in C. elegans . The N ‐glycosylation enzyme Alpha‐mannosidase II is required for dendrite patterning. Alpha‐mannosidase II cell‐autonomously regulates the Menorin adhesion complex. Alpha‐mannosidase II allows decoration of the DMA‐1 receptor with specific N‐ glycans. Specific N ‐glycans on defined DMA‐1 N‐ glycosylation sites pattern dendritic arbors.