PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity.
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.
School of Biochemistry, University of Bristol, Bristol, UK.
Anna
A
Antoniou
Marcio
M
Baptista
Nicholas
N
Carney
Jonathan G
JG
Hanley
D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D054461:Lim Kinases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000378:metabolism
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D002352:Carrier Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; C515892:LIMK1 protein, human; D054461:Lim Kinases