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Journal article
Axonally Synthesized beta-Actin and GAP-43 Proteins Support Distinct Modes of Axonal Growth
The Journal of neuroscience, v 33(8), pp 3311-3322
20 Feb 2013
PMID: 23426659
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Increasing evidence points to the importance of local protein synthesis for axonal growth and responses to axotomy, yet there is little insight into the functions of individual locally synthesized proteins. We recently showed that expression of a reporter mRNA with the axonally localizing beta-actin mRNA 3'UTR competes with endogenous beta-actin and GAP-43 mRNAs for binding to ZBP1 and axonal localization in adult sensory neurons (Donnelly et al., 2011). Here, we show that the 3'UTR of GAP-43 mRNA can deplete axons of endogenous beta-actin mRNA. We took advantage of this 3'UTR competition to address the functions of axonally synthesized beta-actin and GAP-43 proteins. In cultured rat neurons, increasing axonal synthesis of beta-actin protein while decreasing axonal synthesis of GAP-43 protein resulted in short highly branched axons. Decreasing axonal synthesis of beta-actin protein while increasing axonal synthesis of GAP-43 protein resulted in long axons with few branches. siRNA-mediated depletion of overall GAP-43 mRNA from dorsal root ganglia (DRGs) decreased the length of axons, while overall depletion of beta-actin mRNA from DRGs decreased the number of axon branches. These deficits in axon growth could be rescued by transfecting with siRNA-resistant constructs encoding beta-actin or GAP-43 proteins, but only if them RNAs were targeted for axonal transport. Finally, in ovo electroporation of axonally targeted GAP-43 mRNA increased length and axonally targeted beta-actin mRNA increased branching of sensory axons growing into the chick spinal cord. These studies indicate that axonal translation of beta-actin mRNA supports axon branching and axonal translation of GAP-43 mRNA supports elongating growth.
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- Title
- Axonally Synthesized beta-Actin and GAP-43 Proteins Support Distinct Modes of Axonal Growth
- Creators
- Christopher J. Donnelly - Univ Delaware, Dept Biol Sci, Newark, DE 19716 USAMichael Park - Drexel UniversityMirela Spillane - Drexel UniversitySoonmoon Yoo - Alfred I duPont Hosp Children, Wilmington, DE 19803 USAAlmudena Pacheco - Drexel UniversityCynthia Gomes - Drexel Univ, Dept Biol, Philadelphia, PA 19104 USADeepika Vuppalanchi - University of DelawareMarguerite McDonald - Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USAHak Kee Kim - Alfred I duPont Hosp Children, Wilmington, DE 19803 USATanuja T. Merianda - Drexel Univ, Dept Biol, Philadelphia, PA 19104 USAGianluca Gallo - Drexel UniversityJeffery L. Twiss - University of South Carolina
- Publication Details
- The Journal of neuroscience, v 33(8), pp 3311-3322
- Publisher
- Soc Neuroscience
- Number of pages
- 12
- Grant note
- R01NS048090 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Craig H. Neilsen Foundation Miriam and Sheldon G. Adelson Foundation R01-NS041596; R01-NS048090 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Delaware
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000315195700007
- Scopus ID
- 2-s2.0-84874203616
- Other Identifier
- 991021892106004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences