翻译后修饰调控TRPV亚家族通道功能的研究进展
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武汉大学生命科学学院,病毒学国家重点实验室,免疫与代谢前沿科学中心,武汉 430072

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Tel:027-68752148, E-mail: jyao@whu.edu.cnTel: 86-27-68752148, E-mail: jyao@whu.edu.cn

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国家自然科学基金(No.31830031, 31671209, 31871174, 31929003),湖北省自然科学基金(No. 2017CFA063, 2018CFA016)


Research Progress on Post-translational Modification Regulate The Function of TRPV Channel
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State Key Laboratory of Virology, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China

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This work was supported by grants from The National Natural Science Foundation of China (31830031, 31671209, 31871174, 31929003), and Nature Science Foundation of Hubei Province (2017CFA063, 2018CFA016), and the Fundamental Research Funds for the Central Universities.

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    摘要:

    瞬时受体势(transient receptor potential,TRP)通道广泛分布于神经和非神经系统中,响应温度、化学和机械等多种刺激,在机体对外界环境的精确感知中发挥重要功能. 根据蛋白质序列的相似性,哺乳动物中TRP通道家族的27个成员分属TRPA、TRPC、TRPM、TRPML、TRPP和TRPV 6个亚家族. 其中TRPV亚家族包含了6个成员,分别为温度敏感型的TRPV1~4通道,以及对Ca2+具有高选择通透能力的TRPV5和TRPV6通道. 研究结果表明,TRPV亚家族通道参与调控细胞内的离子稳态和信号传导,在温度感知和血管扩张等生理过程中发挥作用,并与癌症、心血管等多种疾病的发生和发展密切相关. 翻译后修饰(post-translational modifications,PTMs)是翻译中或者翻译后在蛋白质特定氨基酸上添加或删减修饰官能团的过程. 越来越多的研究结果表明,TRPV亚家族通道同样可以发生翻译后修饰,并对通道功能产生重要影响. 本文综述了目前已报道的磷酸化、糖基化、泛素化、SUMO化和共价修饰等多种翻译后修饰调控TRPV亚家族成员功能的主要研究进展,以期为进一步研究翻译后修饰对TRPV通道的功能调节提供参考,丰富我们对蛋白质翻译后修饰与生理或病理活动相关性的认识.

    Abstract:

    Transient receptor potential (TRP) channels are widely distributed in nervous and non-nervous systems, responding to thermal, chemical, mechanical and other stimuli. They are emerging as essential sensory molecules that allow animals to respond to environmental changes. The 27 members of the mammalian TRP superfamily are grouped into six subfamilies, the TRPA (ankyrin) family, the TRPC (canonical) family, the TRPM (melastatin) family, the TRPML (mucolipin) family, the TRPP (polycystin) family, and the TRPV (vanilloid) family on the basis of amino acid sequence homology. The TRPV subfamily is composed of six members, TRPV1-6. They can be further divided into two groups, TRPV1-4 subgroup which is weakly Ca2+-selective and highly sensitive to heat, and TRPV5, TRPV6 subgroup which is highly Ca2+-selective and not heat-sensitive. Mounting evidences suggest that TRPV channels are responsible for membrane potential regulation and intracellular Ca2+ signaling, and thus regulate a large number of cellular functions, such as temperature sensation and vasodilation. Dysfunction in channel expression and/or activity has been linked to human disease like cancer and cardiovascular disease. Post-translational modifications (PTMs) involving a functional group being added to a protein, a chemical change in amino acids, and a structural change in the protein have been implicated in regulating activity, localization and interaction with other cellular molecules, thereby increasing the functional diversity of the proteome. Many studies show that TRPV subfamily channels can also undergo post-translational modifications and PTMs have an important impact on channel function. The aim of this review is to address the major advances regarding the various post-translational modifications such as phosphorylation, glycosylation, ubiquitination, SUMOylation, and covalent modification that have been reported to regulate the functions of TRPV channels. Furthermore, we also discussed the possible functions of TRPV channels before and after PTMs in physiological or pathological activities, for a better understanding of the relationship between PTM and physiological or pathological activities.

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杨冰洁,田泉,魏鑫,张豪,姚镜.翻译后修饰调控TRPV亚家族通道功能的研究进展[J].生物化学与生物物理进展,2021,48(2):171-183

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历史
  • 收稿日期:2020-06-06
  • 最后修改日期:2020-07-13
  • 接受日期:2020-07-29
  • 在线发布日期: 2021-04-08
  • 出版日期: 2021-02-20