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. 2016 Jun 29;8:18. doi: 10.3389/fnsyn.2016.00018

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Copyright © 2016 Hong and Park.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Synaptic specificity regulated by non-neuronal factors. (A) Synaptic connectivity of neurons and muscles associated in the egg-laying circuit of C. elegans. HSNL forms synapses with vulval muscle 2 (vm2) and ventral cord (VC) motor neurons, VC4 and VC5 specifically to the regions immediately adjacent to the primary epithelial cells (1°) which secretes SYG-2/Nephrin. Mutations in SYG-1/Neph1 or SYG-2/Nephrin disrupt synaptic specificity of HSNL and cause ectopic synapse formation with select body wall muscle (BWM). Ectopic positioning of SYG-2/Nephrin to the secondary epithelial cells (2°) recruited SYG-1/Neph1 to HSNL near the secondary epithelial cells, which was shown to be sufficient to form synapses ectopically at the sites where SYG-1/Neph1 is recruited (yellow circles). (B) Pathway for HSNL synapse assembly. SYG-2/Nephrin ensures proper localization of SYG-1/Neph1 which defines presynaptic localization of the active zone proteins. ELKS-1/ERC/CAST could function redundantly with SYD-1 or other unidentified presynaptic proteins that positively regulate synapse assembly (gray lines). In the presence of SYD-1, the SYD-2/liprin-α and ELKS-1/ERC/CAST interaction was enhanced (red arrow). In the presence of RSY-1, SYD-1, and ELKS-1/ERC/CAST interaction is weakened (solid green), suggesting RSY-1 as a negative regulator in the HSNL presynaptic assembly process likely by weakening the SYD-2/liprin-α and ELKS-1/ERC/CAST interaction (dotted green) indirectly through the RSY-1 and SYD-1 interaction. Plain lines indicate biochemical interactions. (C) Synaptic connectivity of AIY and RIA interneurons regulated by ventral cephalic sheath cells (CEPshV) at C. elegans nerve ring. Synapses between AIY and RIA are formed en passent as they are ensheathed in zone 2 by CEPshV, which secretes UNC-6/Netrin that regulates UNC-40/DCC activity in AIY. Abnormal distend positioning of CEPshV toward zone 1 causes ectopic localizations of both presynapses (red circles) and UNC-40/DCC (purple triangles) in zone 1 of AIY. (D) Pathways for AIY and RIA connectivity. CEPshV secretes UNC-6/Netrin, which regulates both positioning of presynapses in AIY and axon guidance of postsynaptic RIA through UNC-40/DCC activity to the location specified by CEPshV.