Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling

Rotem Ben Tov Perry, Ella Doron-Mandel, Elena Iavnilovitch, Ida Rishal, Shachar Y. Dagan, Michael Tsoory, Giovanni Coppola, Marguerite K. McDonald, Cynthia Gomes, Daniel H. Geschwind, Jeffery L. Twiss, Avraham Yaron, Mike Fainzilber

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Subcellular localization of mRNA enables compartmentalized regulation within large cells. Neurons are the longest known cells; however, so far, evidence is lacking for an essential role of endogenous mRNA localization in axons. Localized upregulation of Importin β1 in lesioned axons coordinates a retrograde injury-signaling complex transported to the neuronal cell body. Here we show that a long 3@ untranslated region (3@ UTR) directs axonal localization of Importin β1. Conditional targeting of this 3@ UTR region in mice causes subcellular loss of Importin β1 mRNA and protein in axons, without affecting cell body levels or nuclear functions in sensory neurons. Strikingly, axonal knockout of Importin β1 attenuates cell body transcriptional responses to nerve injury and delays functional recovery in vivo. Thus, localized translation of Importin β1 mRNA enables separation of cytoplasmic and nuclear transport functions of importins and is required for efficient retrograde signaling in injured axons.

Original languageEnglish
Pages (from-to)294-305
Number of pages12
JournalNeuron
Volume75
Issue number2
DOIs
StatePublished - 26 Jul 2012
Externally publishedYes

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