Synaptic retinoic acid signaling and homeostatic synaptic plasticity

NEUROPHARMACOLOGY

卷:78

Review

Chen, Lu^1,2  Lau, Anthony G.^1,2  Sarti, Federica^1,2,3 

[1] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

关键词: Retinoic acid;    Homeostatic synaptic plasticity;    Synaptic scaling;    Local protein synthesis;    Retinoic acid receptor alpha;    Fragile-X syndrome;   

DOI  :  10.1016/j.neuropharm.2012.12.004

来源: Elsevier

【 摘 要 】

One of the defining features of the nervous system is its ability to modify synaptic strength in an experience-dependent manner. Chronic elevation or reduction of network activity activates compensatory mechanisms that modulate synaptic strength in the opposite direction (i.e. reduced network activity leads to increased synaptic strength), a process called homeostatic synaptic plasticity. Among the many mechanisms that mediate homeostatic synaptic plasticity, retinoic acid (RA) has emerged as a novel signaling molecule that is critically involved in homeostatic synaptic plasticity induced by blockade of synaptic activity. In neurons, silencing of synaptic transmission triggers RA synthesis. RA then acts at synapses by a non-genomic mechanism that is independent of its well-known function as a transcriptional regulator, but operates through direct activation of protein translation in neuronal dendrites. Protein synthesis is activated by RA-binding to its receptor RARcc, which functions locally in dendrites in a non-canonical manner as an RNA-binding protein that mediate RA's effect on translation. The present review will discuss recent progress in our understanding of the novel role of RA, which led to the identification of RA as a critical synaptic signaling molecule that mediates activity-dependent regulation of protein synthesis in neuronal dendrites. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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