RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression

Title: RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression
Author(s): Puttagunta, R
Schmandke, A
Floriddia, EM
Gaub, P
Fomin, N
Ghyselinck, NB
Di Giovanni, S
Item Type: Journal Article
Abstract: After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane- bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β- dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury. © 2011 Puttagunta et al.
Publication Date: 27-Jun-2011
URI: http://hdl.handle.net/10044/1/21715
DOI: https://dx.doi.org/10.1083/jcb.201102066
ISSN: 0021-9525
Start Page: 1147
End Page: 1156
Journal / Book Title: Journal of Cell Biology
Volume: 193
Issue: 7
Copyright Statement: © 2011 Puttagunta et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Appears in Collections:Department of Medicine
Faculty of Medicine



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