All-trans retinoic acid (RA) is one of several signalling molecules, including oestrogen, progesterone and vitamin D3, that exert their effects by binding to nuclear receptors that act as ligand-activated transcription factors. In this way, RA regulates gene expression programmes that control developmental processes such as limb morphogenesis, anterior-posterior patterning and neurite growth. Jau-Cheng Liou and co-workers now reveal that RA also controls synaptic activity and, surprisingly, does so without affecting gene expression (see ). They show that RA increases the frequency of release of the neurotransmitter acetylcholine from neuromuscular synapses in developing Xenopus neurons in culture. The authors demonstrate that the effect is specific and can be mimicked by agonists of the RA receptor (RAR) RARβ but not RARα/RARγ agonists. In addition, they find that it cannot be blocked by protein synthesis inhibitors. Liou and coworkers therefore conclude that RA acts through RARβ to modulate synaptic transmission by a novel, `nongenomic' mechanism. Since RA and RARs are present at high levels in the embryo, and neuromuscular transmission at synapses is crucial at developing synapses, this could be an important aspect of its developmental role.
