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

EMBO Rep. 2022 Jul 5;23(7):e54163. doi: 10.15252/embr.202154163. Epub 2022 May 19.

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.

Keywords: N-glycans; adhesion; alpha mannosidase II; dendrite; glycosylations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amantadine / metabolism
  • Animals
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Dendrites / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DMA-1 protein, C elegans
  • Membrane Proteins
  • Polysaccharides
  • Amantadine