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.
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Rotem Ben-Tov
authors: RB
authors: Perry
authors: Ella
authors: E
authors: Doron-Mandel
authors: Elena
authors: E
authors: Iavnilovitch
authors: Ida
authors: I
authors: Rishal
authors: Shachar Y
authors: SY
authors: Dagan
authors: Michael
authors: M
authors: Tsoory
authors: Giovanni
authors: G
authors: Coppola
authors: Marguerite K
authors: MK
authors: McDonald
authors: Cynthia
authors: C
authors: Gomes
authors: Daniel H
authors: DH
authors: Geschwind
authors: Jeffery L
authors: JL
authors: Twiss
authors: Avraham
authors: A
authors: Yaron
authors: Mike
authors: M
authors: Fainzilber
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001370:Axonal Transport / Q000235:genetics*; D001369:Axons / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000235:genetics; D012584:Sciatic Nerve / Q000293:injuries; D015398:Signal Transduction / Q000235:genetics; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D028961:beta Karyopherins