apelin受体的翻译后修饰调节其功能表达

IF 3.1 Q2 NEUROSCIENCES AIMS Neuroscience Pub Date : 2023-01-01 DOI:10.3934/neuroscience.2023022
Toshihiko Kinjo, Shun Ebisawa, Tatsuya Nokubo, Mifu Hashimoto, Takonori Yamada, Michiko Oshio, Ruka Nakamura, Kyosuke Uno, Nobuyuki Kuramoto
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引用次数: 0

摘要

& lt; abstract>翻译后修饰(Post-translational modification, PTMs)是发生在蛋白质生物合成之后的蛋白质修饰,在调节蛋白质功能中起着至关重要的作用。它们参与g蛋白偶联受体(gpcr)的功能表达,以及细胞内和分泌蛋白信号传导。在此,我们旨在研究apelin受体(APLNR)的PTMs及其对受体功能的潜在影响。在HEK细胞的体外实验中,我们只观察到糖基化作为APLNR的PTM,以及激动剂(Pyr<sup>1</sup>)-apelin-13的无效受体信号传导。相比之下,在分析小鼠脊髓时,我们检测到糖基化和其他PTMs,不包括异肽。这表明,在体外,额外的PTMs参与了APLNR的功能表达。综上所述,这些发现表明,APLNR在体内需要多个PTMs才能实现功能表达。为了全面了解APLNR的药理作用,有必要建立一个体外系统,充分复制受体的PTM谱。尽管如此,在APLNR研究中克服热敏蛋白水解的挑战是至关重要的。通过阐明ptm的调控,进一步的研究有可能推进apelin/APLNR系统和GPCR信号调节的分析和药理学研究。& lt; / abstract>
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Post-translational modifications of the apelin receptor regulate its functional expression

Post-translational modifications (PTMs) are protein modifications that occur after protein biosynthesis, playing a crucial role in regulating protein function. They are involved in the functional expression of G-protein-coupled receptors (GPCRs), as well as intracellular and secretory protein signaling. Here, we aimed to investigate the PTMs of the apelin receptor (APLNR), a GPCR and their potential influence on the receptor's function. In an in vitro experiment using HEK cells, we only observed glycosylation as a PTM of the APLNR and ineffective receptor signaling by the agonist, (Pyr1)-apelin-13. In contrast, when analyzing mouse spinal cord, we detected glycosylation and other PTMs, excluding isopeptidation. This suggests that additional PTMs are involved in the functional expression of the APLNR in vitro. In summary, these findings suggest that the APLNR in vivo requires multiple PTMs for functional expression. To comprehensively understand the pharmacological effects of the APLNR, it is essential to establish an in vitro system that adequately replicates the receptor's PTM profile. Nonetheless, it is crucial to overcome the challenge of heat-sensitive proteolysis in APLNR studies. By elucidating the regulation of PTMs, further research has the potential to advance the analysis and pharmacological studies of both the apelin/APLNR system and GPCR signal modulation.

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来源期刊
AIMS Neuroscience
AIMS Neuroscience NEUROSCIENCES-
CiteScore
4.20
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: AIMS Neuroscience is an international Open Access journal devoted to publishing peer-reviewed, high quality, original papers from all areas in the field of neuroscience. The primary focus is to provide a forum in which to expedite the speed with which theoretical neuroscience progresses toward generating testable hypotheses. In the presence of current and developing technology that offers unprecedented access to functions of the nervous system at all levels, the journal is designed to serve the role of providing the widest variety of the best theoretical views leading to suggested studies. Single blind peer review is provided for all articles and commentaries.
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