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bioRxiv · 10.1101/238352

Rap2 and TNIK control Plexin-dependent synaptic tiling in C. elegans

Chen, X.·Shibata, A. C.·Weilinger, N. L.·Hendi, A.·Kurashina, M.·Fortes, E.·MacVicar, B.·Murakoshi, H.·Mizumoto, K.
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Abstract

During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, RAP-2 activity is locally suppressed by PLX-1. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.

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Chen, X., Shibata, A. C., Weilinger, N. L., Hendi, A., Kurashina, M., Fortes, E., MacVicar, B., Murakoshi, H., Mizumoto, K.. 2017-12-22. Rap2 and TNIK control Plexin-dependent synaptic tiling in C. elegans. https://doi.org/10.1101/238352

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