Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.
Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.
复制标题
尼罗罗非鱼黑皮质素受体 4 (MC4R) 信号系统
DOI：
10.3390/ijms21197036
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发表时间：
2020-09-24
影响因子：
5.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Liu T;Deng Y;Zhang Z;Cao B;Li J;Sun C;Hu Z;Zhang J;Li J;Wang Y
黑皮质素受体4（MC 4 R）信号系统由MC 4 R、MC 4 R配体[黑素细胞刺激激素（MSH）、促肾上腺皮质激素（ACTH）、刺鼠相关蛋白（AgRP）]和黑皮质素-2受体辅助蛋白2（MRAP 2）组成，在脊椎动物的摄食和生长中发挥重要作用。然而，该系统的表达和功能还没有得到充分的特点，硬骨鱼。本研究克隆了罗非鱼MC 4 R、MRAP 2b、AgRP（AgRP、AgRP 2）和POMCs（POMCa 1、POMCb）基因，并在体外研究了罗非鱼MC 4 R与MRAP 2b、AgRP、α-MSH和ACTH的相互作用。结果表明：(1)罗非鱼MC 4 R、MRAP 2b、AgRP和POMC与它们的哺乳动物对应物共享高氨基酸同一性。(2)通过Co-IP实验证明，罗非鱼MRAP 2b可以与CHO细胞表达的MC 4 R相互作用，从而降低MC 4 R的组成型活性，增强其对ACTH 1 -40的敏感性。(3)在哺乳动物中，AgRP可以作为MC 4 R的反向激动剂和拮抗剂，无论是在MRAP 2b的存在或不存在。这些数据以及MC 4 R、MRAP 2b、AgRP和POMCs在罗非鱼下丘脑中的共表达表明，与哺乳动物一样，ACTH/α-MSH、AgRP和MRAP 2可以与MC 4 R相互作用以控制能量平衡，从而在硬骨鱼的摄食和生长中发挥保守的作用。
The melanocortin receptor 4 (MC4R) signaling system consists of MC4R, MC4R ligands [melanocyte-stimulating hormone (MSH), adrenocorticotropin (ACTH), agouti-related protein (AgRP)], and melanocortin-2 receptor accessory protein 2 (MRAP2), and it has been proposed to play important roles in feeding and growth in vertebrates. However, the expression and functionality of this system have not been fully characterized in teleosts. Here, we cloned tilapia MC4R, MRAP2b, AgRPs (AgRP, AgRP2), and POMCs (POMCa1, POMCb) genes and characterized the interaction of tilapia MC4R with MRAP2b, AgRP, α-MSH, and ACTH in vitro. The results indicate the following. (1) Tilapia MC4R, MRAP2b, AgRPs, and POMCs share high amino acid identity with their mammalian counterparts. (2) Tilapia MRAP2b could interact with MC4R expressed in CHO cells, as demonstrated by Co-IP assay, and thus decrease MC4R constitutive activity and enhance its sensitivity to ACTH1-40. (3) As in mammals, AgRP can function as an inverse agonist and antagonist of MC4R, either in the presence or absence of MRAP2b. These data, together with the co-expression of MC4R, MRAP2b, AgRPs, and POMCs in tilapia hypothalamus, suggest that as in mammals, ACTH/α-MSH, AgRP, and MRAP2 can interact with MC4R to control energy balance and thus play conserved roles in the feeding and growth of teleosts.
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影响因子：
5.2
作者：
Dores RM
通讯作者：
Dores RM
影响因子：
4.1
作者：
Lee, J;Lecaude, S;Dores, RM
通讯作者：
Dores, RM
影响因子：
2.7
作者：
Kobayashi, Yuki;Tsuchlya, Keisuke;Takahashi, Akiyoshi
通讯作者：
Takahashi, Akiyoshi
影响因子：
--
作者：
Josep Agulleiro, Maria;Cortes, Raul;Miguel Cerda-Reverter, Jose
通讯作者：
Miguel Cerda-Reverter, Jose
影响因子：
3
作者：
Alrubaian, J;Danielson, P;Dores, RM
通讯作者：
Dores, RM