| First Author | Puttagunta R | Year | 2011 |
| Journal | J Cell Biol | Volume | 193 |
| Issue | 7 | Pages | 1147-56 |
| PubMed ID | 21690307 | Mgi Jnum | J:174210 |
| Mgi Id | MGI:5052206 | Doi | 10.1083/jcb.201102066 |
| Citation | Puttagunta R, et al. (2011) RA-RAR-{beta} counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression. J Cell Biol 193(7):1147-56 |
| abstractText | 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 beta (RAR-beta), 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-beta 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-beta. Our findings identify a novel link between RA-RAR-beta-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. |
