Research ArticleNeuroscience

The glycosylation pathway is required for the secretion of Slit and for the maintenance of the Slit receptor Robo on axons

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Sci. Signal.  20 Jun 2017:
Vol. 10, Issue 484, eaam5841
DOI: 10.1126/scisignal.aam5841

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Glycosylation and axon guidance

The secreted protein Slit is a repulsive axon guidance cue that binds to the receptor Roundabout (Robo). Manavalan et al. report that Mummy (Mmy), an enzyme of the glycosylation pathway, regulated the Slit-Robo signaling pathway in the developing nervous system of Drosophila melanogaster. In mmy mutants, Slit was not secreted from the midline cells of the ventral nerve cord, resulting in axon guidance defects. In addition, Mmy was also required for maintaining Robo abundance and distribution in axons. Thus, glycosylation affects axon tract establishment and maintenance through mechanisms that affect both the ligand and the receptor.

Abstract

Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor. Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion. Moreover, secretion of Slit was required to maintain the fasciculation and position of longitudinal axon tracts, thus maintaining the hardwiring of the nervous system. Thus, Mmy is required for Slit secretion and for maintaining Robo abundance and distribution in the developing nervous system in Drosophila.

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