Oliet Stéphane H R, Mothet Jean-Pierre
INSERM U378 and Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33077 Bordeaux, France.
Institut de Neurobiologie Alfred Fessard, Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Glia. 2006 Nov 15;54(7):726-737. doi: 10.1002/glia.20356.
Since the late 80s, it is recognized that functional activation of N-methyl D-aspartate receptors (NMDARs) requires the binding of both glutamate and glycine. However, the surprising discovery that the wrong isomer of serine, D-serine, is present in mammals has profoundly challenged this dogmatic model of NMDARs activation. Indeed, there are accumulating evidence indicating that D-serine is the endogenous ligand for the glycine modulatory binding site in many brain areas. D-Serine is synthesized in glial cells by serine racemase (SR) and released upon activation of glutamate receptors. Here, we will provide an overview of recent findings on the molecular and cellular mechanisms involved in the synthesis and release of this gliotransmitter. We will also emphasize the function of this novel messenger in regulating synaptic excitatory transmission and plasticity in different brain areas. Because it fulfils all criteria for a gliotransmitter, D-serine regulatory action on glutamatergic transmission further illustrates the emerging concept of the "tripartite synapse".
自20世纪80年代末以来，人们认识到N-甲基-D-天冬氨酸受体（NMDARs）的功能激活需要谷氨酸和甘氨酸两者结合。然而，令人惊讶的发现是，丝氨酸的错误异构体D-丝氨酸存在于哺乳动物中，这对这种NMDARs激活的教条模型提出了深刻挑战。确实，越来越多的证据表明，D-丝氨酸是许多脑区中甘氨酸调节性结合位点的内源性配体。D-丝氨酸由丝氨酸消旋酶（SR）在胶质细胞中合成，并在谷氨酸受体激活时释放。在此，我们将概述有关这种神经胶质递质合成和释放所涉及的分子和细胞机制的最新发现。我们还将强调这种新型信使在调节不同脑区突触兴奋性传递和可塑性方面的功能。由于它满足神经胶质递质的所有标准，D-丝氨酸对谷氨酸能传递的调节作用进一步说明了“三方突触”这一新兴概念。
