Local synthesis of eukaryotic translation initiation factors EIF2B2 and EIF4G2 regulates axonal growth in rat sympathetic neurons

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIMH	NEURO/BEHAV/SENSYS-14

Authors

• A Kar
• AE Gioio
• BB Kaplan

Abstract

In this study, we investigate the role played by microRNAs (miR) in regulating the local protein synthetic system present in the axon, using primary sympathetic neurons from rat superior cervical ganglion (SCG) cultured in Campenot compartmentalized chambers. A bioinformatic search for putative targets of the axonally enriched microRNA, miR16, revealed the eukaryotic translation initiation factors (EIFs), EIF2B2 and EIF4G2 as candidates. Fluorescence in situ hybridization and metabolic labeling studies showed that EIF2B2 and EIF4G2 mRNAs are present in the axon, and the proteins are locally synthesized. Transfection of precursor miR16 and anti-miR16 into SCG axons showed that miR levels modulate RNA and protein expression of both EIF2B2 and EIF4G2. Interestingly, both miR16- and siRNA-mediated knock-down of EIF2B2 and EIF4G2 led to a decrease in the growth of developing axons. Consistent with these results, siRNA-mediated knock-down of EIF2B2 and EIF4G2 showed a decrease in local axonal protein synthesis, as measured by metabolic labeling assay. These results suggest that local synthesis of EIFs such as EIF2B2 and EIF4G2 in SCG axons can be regulated by microRNAs, and this process plays an important role in axonal growth.

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