Genes Circuits Rhythmes et Neuropathologies, Plasticité du Cerveau, ESPCI Paris, CNRS, PSL University, Paris, France.
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, Bordeaux University, Bordeaux, France.
J Comp Neurol. 2020 Jan 1;528(1):81-94. doi: 10.1002/cne.24742. Epub 2019 Jul 18.
Rhesus glycoproteins (Rh50) have been shown to be ammonia transporters in many species from bacteria to human. They are involved in various physiological processes including acid excretion and pH regulation. Rh50 proteins can also provide a structural link between the cytoskeleton and the plasma membranes that maintain cellular integrity. Although ammonia plays essential roles in the nervous system, in particular at glutamatergic synapses, a potential role for Rh50 proteins at synapses has not yet been investigated. To better understand the function of these proteins in vivo, we studied the unique Rh50 gene of Drosophila melanogaster, which encodes two isoforms, Rh50A and Rh50BC. We found that Drosophila Rh50A is expressed in larval muscles and enriched in the postsynaptic regions of the glutamatergic neuromuscular junctions. Rh50 inactivation by RNA interference selectively in muscle cells caused muscular atrophy in larval stages and pupal lethality. Interestingly, Rh50-deficiency in muscles specifically increased glutamate receptor subunit IIA (GluRIIA) level and the frequency of spontaneous excitatory postsynaptic potentials. Our work therefore highlights a new role for Rh50 proteins in the maintenance of Drosophila muscle architecture and synaptic physiology, which could be conserved in other species.
恒河猴糖蛋白（Rh50）已被证明是许多物种（从细菌到人类）中的氨转运蛋白。它们参与各种生理过程，包括酸排泄和 pH 调节。Rh50 蛋白还可以在维持细胞完整性的细胞骨架和质膜之间提供结构连接。尽管氨在神经系统中起着至关重要的作用，特别是在谷氨酸能突触中，但 Rh50 蛋白在突触中的潜在作用尚未得到研究。为了更好地了解这些蛋白质在体内的功能，我们研究了果蝇（Drosophila melanogaster）特有的 Rh50 基因，该基因编码两种同工型，Rh50A 和 Rh50BC。我们发现果蝇 Rh50A 在幼虫肌肉中表达，并在谷氨酸能神经肌肉接头的突触后区域富集。通过 RNA 干扰选择性地在肌肉细胞中失活 Rh50 会导致幼虫阶段肌肉萎缩和蛹期致死。有趣的是，肌肉中 Rh50 的缺失特异性增加了谷氨酸受体亚基 IIA（GluRIIA）水平和自发性兴奋性突触后电位的频率。因此，我们的工作强调了 Rh50 蛋白在维持果蝇肌肉结构和突触生理学中的新作用，这在其他物种中可能是保守的。
