title: Axonal amphoterin mRNA is regulated by translational control and enhances axon outgrowth.
abstract: High mobility group (HMG) proteins concentrate in the nucleus, interacting with chromatin. Amphoterin is an HMG protein (HMGB1) that has been shown to have extranuclear functions and can be secreted from some cell types. Exogenous amphoterin can increase neurite growth, suggesting that the secreted protein may have growth promoting activities in neurons. Consistent with this, we show that depletion of amphoterin mRNA from cultured adult rat DRG neurons attenuates neurite outgrowth, pointing to autocrine or paracrine mechanisms for its growth-promoting effects. The mRNA encoding amphoterin localizes to axonal processes and we showed recently that its 3'-UTR is sufficient for axonal localization of heterologous transcripts (Donnelly et al., 2013). Here, we show that amphoterin mRNA is transported constitutively into axons of adult DRG neurons. A preconditioning nerve injury increases the levels of amphoterin protein in axons without a corresponding increase in amphoterin mRNA in the axons. A 60 nucleotide region of the amphoterin mRNA 3'-UTR is necessary and sufficient for its localization into axons of cultured sensory neurons. Amphoterin mRNA 3'-UTR is also sufficient for axonal localization in distal axons of DRG neurons in vivo. Overexpression of axonally targeted amphoterin mRNA increases axon outgrowth in cultured sensory neurons, but axon growth is not affected when the overexpressed mRNA is restricted to the cell body.
authors: Department of Anatomy and Neurobiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
authors: Tanuja T
authors: TT
authors: Merianda
authors: Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803.
authors: Jennifer
authors: J
authors: Coleman
authors: Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803.
authors: Hak Hee
authors: HH
authors: Kim
authors: Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208.
authors: Pabitra
authors: P
authors: Kumar Sahoo
authors: Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208.
authors: Cynthia
authors: http://orcid.org/0000-0002-5026-0797
authors: C
authors: Gomes
authors: Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208.
authors: Paul
authors: P
authors: Brito-Vargas
authors: Neuroscience Center, University of Helsinki, 00790 Helsinki, Finland.
authors: Heikki
authors: http://orcid.org/0000-0001-7809-9811
authors: H
authors: Rauvala
authors: Laboratory for Neuroregeneration, Spinal Cord Injury Center, Heidelberg University Hospital, 69118 Heidelberg, Germany and.
authors: Armin
authors: http://orcid.org/0000-0003-1133-1174
authors: A
authors: Blesch
authors: Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803.
authors: Soonmoon
authors: S
authors: Yoo
authors: Department of Anatomy and Neurobiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, twiss@mailbox.sc.edu.
authors: Jeffery L
authors: http://orcid.org/0000-0001-7875-6682
authors: JL
authors: Twiss
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000235:genetics; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D038761:Photobleaching; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000187:drug effects; D014161:Transduction, Genetic
chemical_list: D020413:3' Untranslated Regions; D024243:HMGB1 Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins
keywords: HMGB1; axon regeneration; high mobility group protein; mRNA translation; mRNA transport