Zinc as a translation regulator in neurons: implications for P-body aggregation.
Post-transcriptional mechanisms of gene expression in neuronal cells include mRNA transport and local protein synthesis, which play a vital role in the control of polarity, synaptic plasticity and growth cone motility. RNA-binding proteins, which form the transported ribonucleoparticle (RNP), control mRNA stability and local translation. Recently, the existence of processing bodies (P-bodies), in which mRNA decapping and degradation take place, was revealed in neurons. It was suggested that P-bodies serve as a transient storage compartment for mRNAs, which can be released and, upon stimulation, resume translation. In this study, we focused on the localization of the Dcp1a protein, which serves as a P-body marker, in PC12 growth cones and P19 neuronal cells and its association with the tau mRNA-binding protein HuD. We found that stimulation of neurons by zinc, which is stored and released from synaptic vesicles, caused a disruption of polysomes into monosomes, whereas HuD protein distribution in sucrose gradient fractions remained unaffected. In addition, zinc application caused an aggregation of Dcp1a protein in an RNA-dependent manner. These findings suggest a role for zinc in translation regulation via disruption of polysomes, aggregation of P-bodies in neurons and impairment of the RNP-polysome interaction.
Blumenthal
Jacob
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. jacob.blumenthal@weizmann.ac.il
Ginzburg
Irith
I
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D022083:Cytoplasmic Structures / Q000187:drug effects* / Q000378:metabolism*; D051959:ELAV Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016716:PC12 Cells; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D051959:ELAV Proteins; C406144:IGF2BP1 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D012313:RNA; D004722:Endoribonucleases; C466279:DCP1A protein, human; D015032:Zinc