@article{1f7a39c9368e4b1b97d453d2cb228661,
title = "Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling",
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.",
author = "Perry, {Rotem Ben Tov} and Ella Doron-Mandel and Elena Iavnilovitch and Ida Rishal and Dagan, {Shachar Y.} and Michael Tsoory and Giovanni Coppola and McDonald, {Marguerite K.} and Cynthia Gomes and Geschwind, {Daniel H.} and Twiss, {Jeffery L.} and Avraham Yaron and Mike Fainzilber",
note = "International Foundation for Research in Paraplegia; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Minerva Foundation; Israel Science Foundation; Christopher and Dana Reeve Foundation; NIH [R01-NS041596]We thank Erin Schuman for the myristylated GFP reporter, Freda Miller for the T alpha 1 tubulin promoter, and Fan Wang for the Advilin-Cre mice. We are indebted to Zehava Levy, Vladimir Kiss, Tamara Berkutzki, Golda Damari, and Dena Leshkowitz for excellent professional assistance and to Ozgene Pty (Australia) for assistance in generating the conditional mutant mouse. This work was supported by the International Foundation for Research in Paraplegia, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Minerva Foundation, the Israel Science Foundation, the Christopher and Dana Reeve Foundation, and the NIH (R01-NS041596). M.F. is the incumbent of the Chaya Professorial Chair in Molecular Neuroscience at the Weizmann Institute of Science.",
year = "2012",
month = jul,
day = "26",
doi = "10.1016/j.neuron.2012.05.033",
language = "الإنجليزيّة",
volume = "75",
pages = "294--305",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}