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. Author manuscript; available in PMC: 2015 Jun 1.
Published in final edited form as: Genesis. 2014 Feb 7;52(6):544–554. doi: 10.1002/dvg.22744

FIG. 3. Establishment of AWC asymmetry.

FIG. 3

(a–c) AWC asymmetry is stochastic, and this figure illustrates the case when AWCON is on the left and AWCOFF is on the right. Molecules in red represent AWCOFF promoting, those in green represent AWCON promoting, and those in white indicate inactive or less active molecules. Question marks represent steps in which the molecular mechanism is unknown. Steps in the AWCOFF neuron are proposed to take place sequentially, however the steps in AWCON may not occur in the sequence proposed in the illustration, as the sequence of events has not yet been determined.

Default AWCOFF (right): (a) 1. Calcium enters the cell through voltage-gated calcium channels. 2. Calcium influx stimulates UNC-43 (CaMKII), allowing the assembly of a calcium-signaling complex consisting of UNC-43 (CaMKII), the TIR-1 (Sarm1) adaptor protein, and NSY-1 (MAPKKK). The assembly of the calcium-signaling complex brings these molecules in close proximity of each other, so that UNC-43 (CaMKII) phosphorylates NSY-1 (MAPKKK) and then NSY-1 (MAPKKK) phosphorylates SEK-1 (MAPKK). (b) 3. Microtubules transport the UNC-43 (CaMKII)/TIR-1 (Sarm1)/NSY-1 (MAPKKK) calcium-signaling complex to synapses in AWC axons via an unidentified “X” motor protein. The UNC-104 kinesin motor protein in the contralateral AWC transports an unknown molecule, which is required for the transport of the TIR-1 signaling complex in the AWCOFF cell to specify the AWCOFF subtype. (c) 4. Proposed retrograde signaling, mediated by an unidentified “Y” motor protein, may convey the lateral signaling between the two AWC cells from the synapses to regulate gene expression in the cell body. 5. The AWCOFF marker srsx-3 is transcribed, and the expression of the AWCON marker str-2 is suppressed.

Induced AWCON (left): (a) 1. Axon guidance molecules contribute to AWC axon outgrowth, allowing chemical synapse formation and communication between the two cells. 2. NSY-5 gap junctions and NSY-4 claudin-like adhesions act in parallel to inhibit voltage-gated calcium channels, resulting in a low level of intracellular calcium. (b) 3. NSY-5 and NSY-4 stabilize mature mir-71 miRNA, which inhibits calcium signaling through targeting the 3′ TUR of tir-1/Sarm1. (c) 4. OLRN-1 Raw repeat protein inhibits UNC-43 (CaMKII). 5. The AWCON marker str-2 is expressed, and the AWCOFF marker srsx-3 is inhibited.