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

被引：143

作者：

Andreassi, Catia ^{[1
,2
]}

Zimmermann, Carola ^{[1
,2
]}

Mitter, Richard ^{[3
]}

Fusco, Salvatore ^{[1
,2
]}

Devita, Serena ^{[1
,2
]}

Saiardi, Adolfo ^{[1
,4
]}

Riccio, Antonella ^{[1
,2
]}

机构：

[1] UCL, MRC, Lab Mol & Cell Biol, London, England

[2] UCL, Dept Neurosci Physiol & Pharmacol, London, England

[3] Canc Res UK, London Res Inst, London, England

[4] UCL, MRC, Cell Biol Unit, London, England

来源：

NATURE NEUROSCIENCE | 2010年 / 13卷 / 03期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

LOCAL PROTEIN-SYNTHESIS; TRANSCRIPTION FACTOR; GROWTH CONES; TRANSLATION; ACTIN; LOCALIZATION; LITHIUM; SIGNAL; CREB; MECHANISM;

D O I：

10.1038/nn.2486

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：291 / U6

页数：13

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