法国索邦大学Sabine Lévi和法国艾克斯-马赛大学Christophe Bernard研究团队合作取得一项新突破。他们的研究发现在发育过程中，腺苷和GABA信号协作发挥稳定突触的功能。相关论文于2021年11月5日发表在《科学》杂志上。

研究人员发现虽然突触后GABA A型受体(GABAARs)和腺苷A2A受体 (A2ARs)的激活稳定GABA能突触，但仅A2AR激活就足够了。GABAAR和A2AR依赖性信号通路通过钙-钙调蛋白-腺苷酸环化酶通路的协同作用产生3',5'-单磷酸腺苷。激活的蛋白激酶A磷酸化gephyrin蛋白303位的丝氨酸残基，这是GABAAR稳定所必需的。

最后，突触前和突触后GABA能元件的稳定依赖于gephyrin和突触膜蛋白Slitrk3之间的相互作用。该研究认为A2AR充当活性GABA能突触的探测因子，通过释放GABA、三磷酸腺苷和腺苷以调节它们的命运，使其稳定或消失。

据了解，在发育过程中，神经回路的形成需要稳定的由γ-氨基丁酸激活的(GABAergic)突触并消除不活跃的突触。

附：英文原文

Title: Convergence of adenosine and GABA signaling for synapse stabilization during development

Author: Ferran Gomez-Castro, Stefania Zappettini, Jessica C. Pressey, Carla G. Silva, Marion Russeau, Nicolas Gervasi, Marta Figueiredo, Claire Montmasson, Marianne Renner, Paula M. Canas, Francisco Q. Gonalves, Sofia Alada-Morais, Eszter Szabó, Ricardo J. Rodrigues, Paula Agostinho, Angelo R. Tomé, Ghislaine Caillol, Olivier Thoumine, Xavier Nicol, Christophe Leterrier, Rafael Lujan, Shiva K. Tyagarajan, Rodrigo A. Cunha, Monique Esclapez, Christophe Bernard, Sabine Lévi

Issue&Volume: 2021-11-05

Abstract: During development, neural circuit formation requires the stabilization of active γ-aminobutyric acid–mediated (GABAergic) synapses and the elimination of inactive ones. Here, we demonstrate that, although the activation of postsynaptic GABA type A receptors (GABAARs) and adenosine A2A receptors (A2ARs) stabilizes GABAergic synapses, only A2AR activation is sufficient. Both GABAAR- and A2AR-dependent signaling pathways act synergistically to produce adenosine 3′,5′-monophosphate through the recruitment of the calcium–calmodulin–adenylyl cyclase pathway. Protein kinase A, thus activated, phosphorylates gephyrin on serine residue 303, which is required for GABAAR stabilization. Finally, the stabilization of pre- and postsynaptic GABAergic elements involves the interaction between gephyrin and the synaptogenic membrane protein Slitrk3. We propose that A2ARs act as detectors of active GABAergic synapses releasing GABA, adenosine triphosphate, and adenosine to regulate their fate toward stabilization or elimination.

DOI: abk2055

Source: https://www.science.org/doi/10.1126/science.abk2055