Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal, Consejo Superior de Investigaciones Científicas, Ribera de Cabanes, Castellón, Spain.
Mol Cell Endocrinol. 2010 May 14;320(1-2):145-52. doi: 10.1016/j.mce.2010.01.032. Epub 2010 Feb 6.
In this paper, we identify three different MRAPs in zebrafish, zfMRAP1, zfMRAP2a and zfMRAP2b, and demonstrate that zfMC2R is not functional in the absence of MRAP expression. ZfMRAP1 expression was restricted to adipose tissue and the anterior kidney whereas MRAP2a and MRAP2b were expressed in all the tissues tested. Quantification of surface receptor and immunofluorescence studies indicated that the receptor is unable to translocate to membrane in the absence of MRAP isoforms. MRAP1 and MRAP2b are localized in the plasma membrane in the absence of zfMC2R expression but MRAP2b is retained in perinuclear position. MRAP1 and MRAP2a displayed an equivalent translocation capacity to the membrane of zfMC2R but only zfMRAP1 expression led to intracellular cAMP increases after ACTH stimulation. ZfMRAP2b had no effect on zfMC2R activity but both zfMRAP2 isoforms enhanced the zfMRAP1-assisted cAMP intracellular increase, suggesting an interaction between zfMRAP1 and zfMRAP2s when regulating zfMC2R activity.
在本文中，我们鉴定了三种不同的斑马鱼 MRAP，即 zfMRAP1、zfMRAP2a 和 zfMRAP2b，并证明在没有 MRAP 表达的情况下，zfMC2R 没有功能。zfMRAP1 的表达局限于脂肪组织和前肾，而 MRAP2a 和 MRAP2b 在所有测试的组织中均有表达。表面受体的定量和免疫荧光研究表明，在没有 MRAP 同工型的情况下，该受体无法向膜移位。在没有 zfMC2R 表达的情况下，MRAP1 和 MRAP2b 定位于质膜，但 MRAP2b 保留在核周位置。MRAP1 和 MRAP2a 显示出与 zfMC2R 膜相同的易位能力，但只有 zfMRAP1 的表达在 ACTH 刺激后导致细胞内 cAMP 增加。zfMRAP2b 对 zfMC2R 活性没有影响，但两种 zfMRAP2 同工型均增强了 zfMRAP1 辅助的细胞内 cAMP 增加，表明在调节 zfMC2R 活性时，zfMRAP1 和 zfMRAP2s 之间存在相互作用。
