RT Journal Article SR Electronic T1 Rap2 and TNIK control Plexin-dependent synaptic tiling in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 238352 DO 10.1101/238352 A1 Xi Chen A1 Akihiro C.E. Shibata A1 Ardalan Hendi A1 Mizuki Kurashina A1 Ethan Fortes A1 Nicholas L Weilinger A1 Brian MacVicar A1 Hideji Murakoshi A1 Kota Mizumoto YR 2018 UL http://biorxiv.org/content/early/2018/05/31/238352.abstract 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 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.