Abstract
Plexins exhibit multitudinous, evolutionarily conserved functions in neural development. How Plexins employ their diverse structural motifs in vivo to perform distinct roles is unclear. We previously reported that Plexin B (PlexB) controls multiple steps during the assembly of the Drosophila olfactory circuit (Li et al., 2018b). Here, we systematically mutagenized structural motifs of PlexB and examined the function of these variants in these multiple steps: axon fasciculation, trajectory choice, and synaptic partner selection. We found that the extracellular Sema domain is essential for all three steps, 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, the divergent roles of PlexB motifs in distinct steps of neural development contribute to its functional versatility in neural circuit assembly.
Highlights
Nervous systems are composed of intricately structured assemblies of neurons
We recently reported that Plexin B (PlexB) plays indispensable roles in multiple steps during the assembly of the Drosophila olfactory map, with level-independent functions in the axon fasciculation of olfactory receptor neurons (ORNs) and level-dependent tasks in ORN axon trajectory choice and subsequent glomerular targeting (Li et al, 2018b)
Sema Domain The extracellular Sema domain is a molecular signature of Plexins and Semaphorins – the canonical Plexin ligands
Summary
Nervous systems are composed of intricately structured assemblies of neurons. Their proper function requires highly specified circuit organization, wherein neurons make precise connections with their synaptic partners. The study of neural circuit assembly has generated an ever-expanding catalog of wiring molecules, whose biological roles ensure the fidelity of neuronal connections and of information transmission Even for Plexins, we have sparse knowledge on the connection between their structural motifs and their in vivo cellular functions, especially in the context of multi-step neural circuit assembly
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