First Author | Perry RB | Year | 2012 |
Journal | Neuron | Volume | 75 |
Issue | 2 | Pages | 294-305 |
PubMed ID | 22841314 | Mgi Jnum | J:222342 |
Mgi Id | MGI:5644383 | Doi | 10.1016/j.neuron.2012.05.033 |
Citation | Perry RB, et al. (2012) Subcellular knockout of importin beta1 perturbs axonal retrograde signaling. Neuron 75(2):294-305 |
abstractText | 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 beta1 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 beta1. Conditional targeting of this 3' UTR region in mice causes subcellular loss of Importin beta1 mRNA and protein in axons, without affecting cell body levels or nuclear functions in sensory neurons. Strikingly, axonal knockout of Importin beta1 attenuates cell body transcriptional responses to nerve injury and delays functional recovery in vivo. Thus, localized translation of Importin beta1 mRNA enables separation of cytoplasmic and nuclear transport functions of importins and is required for efficient retrograde signaling in injured axons. |