An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons

Catia Andreassi, Carola Zimmermann, Richard Mitter, Salvatore Fusco, Serena Devita, Adolfo Saiardi, Antonella Riccio

Research output: Contribution to journalArticlepeer-review

Abstract

mRNA localization is an evolutionary conserved mechanism that underlies the establishment of cellular polarity and specialized cell functions. To identify mRNAs localized in subcellular compartments of developing neurons, we took an original approach that combines compartmentalized cultures of rat sympathetic neurons and sequential analysis of gene expression (SAGE). Unexpectedly, the most abundant transcript in axons was mRNA for myo-inositol monophosphatase-1 (Impa1), a key enzyme that regulates the inositol cycle and the main target of lithium in neurons. A novel localization element within the 3′ untranslated region of Impa1 mRNA specifically targeted Impa1 transcript to sympathetic neuron axons and regulated local IMPA1 translation in response to nerve growth factor (NGF). Selective silencing of IMPA1 synthesis in axons decreased nuclear CREB activation and induced axonal degeneration. These results provide insights into mRNA transport in axons and reveal a new NGF-responsive localization element that directs the targeting and local translation of an axonal transcript.

Original languageEnglish
Pages (from-to)291-301
Number of pages11
JournalNature Neuroscience
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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