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N-Acetylaspartylglutamate Synthetase II Synthesizes N-Acetylaspartylglutamylglutamate

机译:N-乙酰丙酮酰谷氨酸合成酶II合成N-乙酰丙酮酰谷氨酸谷氨酸

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摘要

N-Acetylaspartylglutamate (NAAG) is found at high concentrations in the vertebrate nervous system. NAAG is an agonist at group II metabotropic glutamate receptors. In addition to its role as a neuropeptide, a number of functions have been proposed for NAAG, including a role as a non-excitotoxic transport form of glutamate and a molecular water pump. We recently identified a NAAG synthetase (now renamed NAAG synthetase I, NAAGS-I), encoded by the ribosomal modification protein rimK-like family member B (Rimklb) gene, as a member of the ATP-grasp protein family. We show here that a structurally related protein, encoded by the ribosomal modification protein rimK-like family member A (Rimkla) gene, is another NAAG synthetase (NAAGS-II), which in addition, synthesizes the N-acetylated tripeptide N-acetylaspartylglutamylglutamate (NAAG2). In contrast, NAAG2 synthetase activity was undetectable in cells expressing NAAGS-I. Furthermore, we demonstrate by mass spectrometry the presence of NAAG2 in murine brain tissue and sciatic nerves. The highest concentrations of both, NAAG2 and NAAG, were found in sciatic nerves, spinal cord, and the brain stem, in accordance with the expression level of NAAGS-II. To our knowledge the presence of NAAG2 in the vertebrate nervous system has not been described before. The physiological role of NAAG2, e.g. whether it acts as a neurotransmitter, remains to be determined.
机译:在脊椎动物神经系统中发现了高浓度的N-乙酰丙酮酰谷氨酸(NAAG)。 NAAG是II组代谢型谷氨酸受体的激动剂。除了其作为神经肽的作用外,还提出了NAAG的许多功能,包括作为谷氨酸的非兴奋性转运形式和分子水泵的作用。我们最近鉴定了由核糖体修饰蛋白rimK样家族成员B(Rimklb)基因编码的NAAG合成酶(现更名为NAAG合成酶I,NAAGS-1)作为ATP抓取蛋白家族的成员。我们在这里显示,由核糖体修饰蛋白rimK样家族成员A(Rimkla)基因编码的结构相关蛋白是另一种NAAG合成酶(NAAGS-II),此外,它还合成了N-乙酰化三肽N-乙酰基天冬氨酰谷氨酰胺基谷氨酸( NAAG2)。相反,在表达NAAGS-1的细胞中未检测到NAAG2合成酶活性。此外,我们通过质谱法证明了鼠脑组织和坐骨神经中NAAG2的存在。根据NAAGS-II的表达水平,在坐骨神经,脊髓和脑干中发现了NAAG2和NAAG的最高浓度。据我们所知,以前没有描述过脊椎动物神经系统中NAAG2的存在。 NAAG2的生理作用,例如它是否充当神经递质,还有待确定。

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