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


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 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.

SUBMITTER: Chen X 

PROVIDER: S-EPMC6067881 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in <i>C. elegans</i>.

Chen Xi X   Shibata Akihiro Ce AC   Hendi Ardalan A   Kurashina Mizuki M   Fortes Ethan E   Weilinger Nicholas L NL   MacVicar Brian A BA   Murakoshi Hideji H   Mizumoto Kota K  

eLife 20180731


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 (<i>rap-2</i>) and its effector, TNIK (<i>mig-15</i>), act genetically downstream of Plexin (<i>plx-1</i>) to restrict presynaptic assembly and to form tiled synaptic inne  ...[more]

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