翻译后修饰调控TRPV亚家族通道功能的研究进展

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...

Research Progress on Post-translational Modification Regulate The Function of TRPV Channel

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.