Insight into molecular and functional diversity of tachykinins and their receptors.
Insight into molecular and functional diversity of tachykinins and their receptors.
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DOI：
10.2174/0929866511320060002
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发表时间：
2013-05
影响因子：
1.6
通讯作者：
H. Satake;M. Aoyama;T. Sekiguchi;T. Kawada
中科院分区：
文献类型：
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作者：
H. Satake;M. Aoyama;T. Sekiguchi;T. Kawada
速激肽（Tachykinins，TKs）及其结构相关肽是动物界中最大的肽超家族。TK已被证明发挥各种生理作用，不仅作为主要的脑/肠肽，而且作为脊索动物的内分泌/旁分泌激素和两栖动物的外分泌因子。近年来的研究还表明，TK作为脑/肠肽和内分泌/旁分泌因子的生物学功能在原脊索动物中基本上是保守的，哺乳动物TK基因的选择性剪接机制是在脊椎动物进化过程中建立起来的。原口动物具有两种结构和功能不同的肽;无脊椎动物TK（inv-TK）作为从几种生物的唾液腺分泌的毒素样化合物，而TK相关肽（TKRP）是脊索动物TK的功能对应物。此外，在双胚层生物体中检测到TKRP样序列。TKRP前体和脊索动物TK前体在结构组织上的巨大差异清楚地表明了TK和TKRP的不同进化过程。尽管具有高度的序列同源性，但TK受体对其内源性配体表现出选择性亲和力，而TKRP对其受体表现出冗余活性。此外，除了作为脑/肠肽的伤害感受、炎症和收缩作用之外，许多研究已经揭示了TK对下丘脑和生殖器官的新的生物学作用，揭示了TK作为生殖的关键调节剂的生物学作用。这些发现揭示了TK/TKRP超家族及其受体的结构和功能的复杂进化谱系。在这篇综述中，我们提出的TK/TKRP超家族的基本知识和最新的各种观点。
Tachykinins (TKs) and their structurally related peptides constitute the largest peptide superfamily in the animal kingdom. TKs have been shown to play various physiological roles not only as major brain/gut peptides but also as endocrine/paracrine hormones in chordates and exocrine factors in amphibians. Recent studies have also revealed that the biological roles of TKs as brain/gut peptides and endocrine/paracrine factors are essentially conserved in protochordates, and that alternative splicing mechanism in mammalian TK genes were established during the evolution of vertebrates. Protostomes possess two structurally and functionally different peptides; invertebrate TKs (inv-TKs) serve as toxin-like compounds secreted from the salivary gland of several organisms, whereas TK-related peptides (TKRPs) are functional counterparts for chordate TKs. Additionally, a TKRP-like sequence was detected in a diploblastic organism. The dramatic difference in structural organizations between TKRP precursors and chordate TK precursors clearly indicates the distinct evolutionary processes of TKs and TKRPs. Despite high sequence homology, TK receptors manifest selective affinity to their endogenous ligands, while TKRPs exhibit redundant activity at their receptors. Moreover, in addition to nociceptive, inflammatory, and contractile effects as brain/gut peptides, a number of studies have revealed novel biological effects of TKs on the hypothalamus and genital organs, revealing the biological roles of TKs as pivotal regulators of reproduction. These findings shed light on complicated evolutionary lineages of both structures and functions of the TK/TKRP superfamily and their receptors. In this review, we present basic and latest knowledge of the TK/TKRP superfamily with various points of view.