Journal article
Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling
Neuron (Cambridge, Mass.), v 75(2), pp 294-305
26 Jul 2012
PMID: 22841314
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
► Knockout of a localizing UTR region selectively depletes Importin β1 from axons
► Axon-specific knockout of Importin β1 perturbs cell body responses to axotomy
► Localized axonal translation is required for efficient retrograde injury signaling
► mRNA localization allows compartmentalization of distinct importin functions
Perry et al. target a 3′ UTR of Importin β1, leading to specific loss of the protein in axons, without affecting neuronal cell bodies. This subcellular knockout perturbs injury responses, and thus localized translation in axons is required for retrograde axonal signaling.
Metrics
Details
- Title
- Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling
- Creators
- Rotem Ben-Tov Perry - Weizmann Institute of ScienceElla Doron-Mandel - Weizmann Institute of ScienceElena Iavnilovitch - Weizmann Institute of ScienceIda Rishal - Weizmann Institute of ScienceShachar Y. Dagan - Weizmann Institute of ScienceMichael Tsoory - Weizmann Institute of ScienceGiovanni Coppola - University of California, Los AngelesMarguerite K. McDonald - University of DelawareCynthia Gomes - Department of Biology, Drexel University, Philadelphia, PA 19104, USADaniel H. Geschwind - University of California, Los AngelesJeffery L. Twiss - Drexel UniversityAvraham Yaron - Weizmann Institute of ScienceMike Fainzilber - Weizmann Institute of Science
- Publication Details
- Neuron (Cambridge, Mass.), v 75(2), pp 294-305
- Publisher
- Elsevier
- Number of pages
- 12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000307033200014
- Scopus ID
- 2-s2.0-84864296464
- Other Identifier
- 991021892105604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences