In C. elegans, six GABAergic neurons (named DD neurons) rewire during development by reversing their axonal and dendritic domains without other obvious morphological transitions. This unique event provides an attractive system in which we can identify the molecular requirements of circuit remodeling. We have previously identified the conserved gene
myrf-1 and its paralog
myrf-2 as key positive regulators of DD neuron rewiring. Using immunoprecipitation of GFP::MYRF-1 from C. elegans tissues followed by quantitative mass spectrometry analyses, we have identified PAN-1 (P-granule Associated Novel protein), a novel leucine rich repeat (LRR) domain-containing protein, as an interactor of MYRF in vivo.
pan-1 null mutants exhibit blocked synaptic rewiring in DD neurons. The membrane-associated isoform of PAN-1B rescues synaptic rewiring cell-autonomously. Over-expression of MYRF restores the rewiring defect of
pan-1(0) mutants, indicating that PAN-1 acts upstream of MYRF.