Formation and maintenance of neural circuit

The wiring of functional neural network results from accurate synaptic matching enabled by precise targeting of axons and dendrites. During the development of Drosophila olfactory system, the axon of sensory neuron (olfactory receptor neuron; ORN) and the dendrites of second-order neuron (projection neuron; PN) target one of ~50 glomeruli in the antennal lobe (AL), resulting in one-to-one specific connections of proper synaptic partners.
To elucidate the molecular mechanism underlying PN dendrite targeting, we performed MARCM-based genetic screen and identified an evolutionarily conserved protein, Strip (Striatin-interacting protein). By using Drosophila genetic and biochemical methods, we found that loss of strip gene exhibited the defects in dendrite branching and axon elongation. Furthermore, we uncovered that Strip forms a complex with molecules involved in intracellular trafficking such as Dynactin component Glued and Rab5 GEF Sprint, thus Strip contributes to the proper trafficking of proteins in neuronal cells, which is essential for the neuronal morphogenesis. Further investigation of the Strip function may lead to an understanding of the detailed molecular mechanism of neural circuit formation and the cause of the neurodegenerative diseases in the future.



References
Okumura, M., Sakuma, C., Miura, M. and Chihara, T.: Linking cell surface receptors to microtubules: Tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis. J Neurosci 35, 1979-1990, 2015
Sakuma, C., Kawauchi, T., Haraguchi, S., Shikanai, M., Yamaguchi, Y., Gelfand, V.I., Luo, L. and Miura, M. and Chihara, T.: Drosophila Strip serves as a platform for early endosome organization during axon elongation. Nat Commun 5, 5180, 2014
Sekine, S.U., Haraguchi, S., Chao, K., Kato, T., Luo, L., Miura, M. and Chihara, T.: Meigo governs dendrite targeting specificity by modulating Ephrin level and N-glycosylation. Nat Neurosci, 16, 683-91, 2013
Chihara, T., Luginbuhl, D. and Luo, L.: Cytoplasmic and mitochondrial protein translation in axonal and dendritic terminal arborization. Nat Neurosci. 10, 828-837, 2007


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