Functional divergence of Plexin B structural motifs in distinct steps of Drosophila olfactory circuit assembly

Abstract

Plexins exhibit multitudinous, evolutionarily conserved functions in the development of nervous systems. However, how Plexins employ their diverse structural motifs in vivo to perform distinct roles in the stepwise assembly of neural circuits is unclear. Here, we systematically mutagenized structural motifs of Drosophila Plexin B (PlexB) and examined the function of these variants at multiple PlexB-mediated neurodevelopmental processes in olfactory receptor neurons: axon fasciculation, trajectory choice, and synaptic partner selection. We found that the extracellular Sema domain is essential for all three processes, the catalytic site of the intracellular RapGAP is engaged in none, and the intracellular GTPase-binding motifs are essential for trajectory choice and synaptic partner selection, but are dispensable for fasciculation. Moreover, extracellular PlexB cleavage serves as a regulatory mechanism of PlexB signaling. Thus, PlexB structural motifs have divergent roles in distinct steps of neural development, altogether contributing to the functional versatility of PlexB in neural circuit assembly.