Galiano Mauricio R, Goitea Victor E, Hallak Marta E
Centro de Investigaciones de Química Biológica de Córdoba, CIQUIBIC, Departamento de Química Biológica, Facultad de Ciencias Químicas, CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.
J Neurochem. 2016 Aug;138(4):506-17. doi: 10.1111/jnc.13708. Epub 2016 Jul 5.
Post-translational arginylation of proteins is an important regulator of many physiological pathways in cells. This modification was originally noted in protein degradation during neurodegenerative processes, with an apparently different physiological relevance between central and peripheral nervous system. Subsequent studies have identified a steadily increasing number of proteins and proteolysis-derived polypeptides as arginyltransferase (ATE1) substrates, including β-amyloid, α-synuclein, and TDP43 proteolytic fragments. Arginylation is involved in signaling processes of proteins and polypeptides that are further ubiquitinated and degraded by the proteasome. In addition, it is also implicated in autophagy/lysosomal degradation pathway. Recent studies using mutant mouse strains deficient in ATE1 indicate additional roles of this modification in neuronal physiology. As ATE1 is capable of modifying proteins either at the N-terminus or middle-chain acidic residues, determining which proteins function are modulated by arginylation represents a big challenge. Here, we review studies addressing various roles of ATE1 activity in nervous system function, and suggest future research directions that will clarify the role of post-translational protein arginylation in brain development and various neurological disorders. Arginyltransferase (ATE1), the enzyme responsible for post-translational arginylation, modulates the functions of a wide variety of proteins and polypeptides, and is also involved in the main degradation pathways of intracellular proteins. Regulatory roles of ATE1 have been well defined for certain organs. However, its roles in nervous system development and neurodegenerative processes remain largely unknown, and present exciting opportunities for future research, as discussed in this review.
蛋白质的翻译后精氨酰化是细胞中许多生理途径的重要调节因子。这种修饰最初是在神经退行性过程中的蛋白质降解中被发现的，在中枢神经系统和外周神经系统之间具有明显不同的生理相关性。随后的研究发现，越来越多的蛋白质和蛋白水解衍生多肽是精氨酰转移酶（ATE1）的底物，包括β-淀粉样蛋白、α-突触核蛋白和TDP43蛋白水解片段。精氨酰化参与蛋白质和多肽的信号传导过程，这些蛋白质和多肽会进一步被泛素化并通过蛋白酶体降解。此外，它还与自噬/溶酶体降解途径有关。最近使用缺乏ATE1的突变小鼠品系进行的研究表明，这种修饰在神经元生理学中还有其他作用。由于ATE1能够在N端或中链酸性残基处修饰蛋白质，确定哪些蛋白质功能受精氨酰化调节是一个巨大的挑战。在这里，我们综述了关于ATE1活性在神经系统功能中的各种作用的研究，并提出了未来的研究方向，这将阐明翻译后蛋白质精氨酰化在脑发育和各种神经疾病中的作用。精氨酰转移酶（ATE1）是负责翻译后精氨酰化的酶，它调节多种蛋白质和多肽的功能，还参与细胞内蛋白质的主要降解途径。ATE1在某些器官中的调节作用已经得到了很好的定义。然而，它在神经系统发育和神经退行性过程中的作用仍然很大程度上未知，正如本综述所讨论的，这为未来的研究提供了令人兴奋的机会。
