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.

journal_name

Elife

journal_title

eLife

authors

Chen X,Shibata AC,Hendi A,Kurashina M,Fortes E,Weilinger NL,MacVicar BA,Murakoshi H,Mizumoto K

doi

10.7554/eLife.38801

subject

Has Abstract

pub_date

2018-07-31 00:00:00

issn

2050-084X

pii

38801

journal_volume

7

pub_type

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