PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity.

Anna Antoniou,Marcio Baptista,Jonathan G Hanley,Nicholas Carney

doi:10.1002/embr.201337631

Abstract

MicroRNAs fine-tune gene expression by inhibiting the translation of mRNA targets. Argonaute (Ago) proteins are critical mediators of microRNA-induced post-transcriptional silencing and have been shown to associate with endosomal compartments, but the molecular mechanisms that underlie this process are unclear, especially in neurons. Here, we report a novel interaction between Ago2 and the BAR-domain protein, PICK1. We show that PICK1 promotes Ago2 localization at endosomal compartments in neuronal dendrites and inhibits Ago2 function in translational repression following neuronal stimulation. We propose that PICK1 provides a link between activity-dependent endosomal trafficking and local regulation of translation in neurons.

Highlights

MicroRNAs are small RNA species encoded in the genome that associate with Argonaute proteins in the RNA-induced silencing complex (RISC) and mediate post-transcriptional silencing of one or more messenger RNA targets [1,2]
As PICK1 associates with endosomes and regulates endosomal trafficking [14,15,16] and Argonaute 2 (Ago2) associates with intracellular membranes [9,10,23,24], we investigated the colocalization of Ago2 with PICK1 at endosomal compartments
As PICK1 plays a critical role in synaptic plasticity and is well characterized for its role in long-term depression (LTD) [17], we explored the effects of neuronal stimulation on the association of PICK1 and Ago2 in neurons

Summary

Introduction

MicroRNAs (miRNAs) are small RNA species encoded in the genome that associate with Argonaute proteins in the RNA-induced silencing complex (RISC) and mediate post-transcriptional silencing of one or more messenger RNA (mRNA) targets [1,2]. A PICK1 and Ago2 colocalize in Rab11-positive endosomal compartments in COS7 cells. Cells expressing GFP-Ago2 and mCherry-PICK1 were stained using specific antibodies against Rab11, EEA1, or Dcp1a (blue channel).

Results

Conclusion