Neural circuit assembly requires precise dendrite and axon targeting. In this study, a research group at the University of Tokyo (Dr. Chihara and Dr. Sekine et al.) and Stanford University (Dr. Luo) identified an evolutionarily conserved endoplasmic reticulum (ER) protein, Meigo, from a mosaic genetic screen in the fruit fly, Drosophila melanogaster.
By using the olfactory neural circuit of Drosophila, they revealed that Meigo is cell-autonomously required in olfactory neurons to target their axons and dendrites to the appropriate synaptic site and to refine their dendrite innervation.
Loss of Meigo induces an unfolded protein response and reduces the amount of neuronal cell surface proteins including Ephrin. Ephrin is a well-known cell surface protein involved in neural network formation. Ephrin overexpression specifically suppresses the dendrite refinement defect of meigo mutant, and ephrin knockdown causes a dendrite refinement defect similar to that of meigo mutant neuron.
Furthermore, they revealed that Meigo positively regulates the level of Ephrin N-glycosylation, which is required for its optimal function in vivo. Thus, Meigo, an ER-resident protein, governs neuronal targeting specificity by regulating ER folding capacity and protein N-glycosylation. Further, Ephrin appears to be a key substrate that mediates Meigo’s function in the refinement of dendrite targeting..
Source: University of Tokyo