TY - JOUR TI - Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans AU - Chen, Xi AU - Shibata, Akihiro CE AU - Hendi, Ardalan AU - Kurashina, Mizuki AU - Fortes, Ethan AU - Weilinger, Nicholas L AU - MacVicar, Brian A AU - Murakoshi, Hideji AU - Mizumoto, Kota A2 - Sengupta, Piali A2 - VijayRaghavan, K VL - 7 PY - 2018 DA - 2018/07/31 SP - e38801 C1 - eLife 2018;7:e38801 DO - 10.7554/eLife.38801 UR - https://doi.org/10.7554/eLife.38801 AB - 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 genetically 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, PLX-1 suppresses local RAP-2 activity. 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. KW - synapse KW - development KW - plexin KW - pattern formation KW - RAP2 KW - genetics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -