Retrograde Signaling

Aex-1 Acts Presynaptically

Science's STKE  29 Jan 2002:
Vol. 2002, Issue 117, pp. tw45
DOI: 10.1126/stke.2002.117.tw45

Mutants in the aex-1 gene were identified in a screen for worms with an abnormal defecation motor program. Doi and Iwasaki isolated the aex-1 gene, and it encoded a novel protein with a calcium-binding C2 domain and with limited sequence similarity to a synaptic protein Munc13. The aex-1 worms were resistant to paralysis induced by an acetylcholinesterase inhibition (aldicarb resistance), suggesting a defect in synaptic transmission. An AEX-1-green fluorescent protein (GFP) reporter showed aex-1 expression in muscles and intestine, predominantly. Selective expression of aex-1 in intestine rescued the defecation defect, and selective expression in muscle rescued the aldicarb resistance phenotype. Neuron-specific expression did not rescue any of the measured phenotypes, which suggests a presynaptic role for aex-1. Analysis of aex-1 mutants in combination with mutations that activate presynaptic neurotransmitter release suppress the aex-1 aldicarb resistance phenotype. Further characterization of the neuromuscular junction phenotypes associated with aex-1 showed that most presynaptic proteins appeared unaffected in terms of localization with one exception--unc13 was more diffusely distributed in aex-1 than in wild-type worms. Again, muscle-specific, but not neuronal, expression of aex-1 rescued decreased body thrashing and the diffuse unc13 localization phenotypes. Finally, a genetic interaction between aex-1 and a putative prohormone convertase gene aex-5 was tested. They produced the same neuromuscular junction phenotypes as single or double mutants, suggesting they act in the same pathway. AEX-1, thus, appears to be a new player controlling release of retrograde signals that influence presynaptic function.

M. Doi, K. Iwasaki, Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1. Neuron 33, 249-259 (2002). [Online Journal]

M. L. Nonet, AEXpulsing a retrograde signal. Neuron 33, 155-156 (2002). [Online Journal]