The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface.
The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface.
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家族性糖皮质激素缺乏症 1 型中发现的大多数促肾上腺皮质激素受体（黑皮质素 2 受体）突变会导致受体向细胞表面的运输缺陷。
DOI：
10.1210/jc.2008-1744
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发表时间：
2008-12
影响因子：
5.8
通讯作者：
Clark, A. J. L.
中科院分区：
文献类型：
--
作者：
Chung, T. T.;Webb, T. R.;Chan, L. F.;Cooray, S. N.;Metherell, L. A.;King, P. J.;Chapple, J. P.;Clark, A. J. L.
在ACTH受体（黑皮质素2受体，MC 2 R）中发现了至少24种错义、非保守突变，这些突变与常染色体隐性遗传疾病家族性糖皮质激素缺乏症（FGD）1型相关。这些突变的表征受到了建立MC 2 R功能性异源细胞转染系统的困难的阻碍。最近，黑皮质素2受体辅助蛋白（MRAP）被确定为必需的运输MC 2 R的细胞表面，因此，MC 2 R突变的功能表征现在是可能的。阐明FGD中MC 2 R功能缺陷的分子机制。建立表达人MRAPα的稳定细胞系，并用野生型或突变型MC 2 R瞬时转染。采用细胞表面表达测定、cAMP报告基因测定、共聚焦显微镜和MRAPα免疫共沉淀法对突变MC 2 R进行功能表征。尽管MRAPα与所有突变体相互作用，但所有MC 2 R突变中有三分之二的细胞表面运输显著减少。对那些到达细胞表面的突变受体的分析表明，在用ACTH刺激后，4/6未能发出信号。在FGD中发现的大多数MC 2 R突变不能发挥作用，因为它们不能运输到细胞表面。
There are at least twenty-four missense, non-conservative mutations found in the ACTH receptor (Melanocortin 2 receptor, MC2R) which have been associated with the autosomal recessive disease Familial Glucocorticoid Deficiency (FGD) type 1. The characterization of these mutations has been hindered by difficulties in establishing a functional heterologous cell transfection system for MC2R. Recently the melanocortin 2 receptor accessory protein (MRAP) was identified as essential for trafficking of MC2R to the cell surface; therefore a functional characterization of MC2R mutations is now possible. To elucidate the molecular mechanisms responsible for defective MC2R function in FGD. Stable cell lines expressing human MRAPα were established and transiently transfected with wild-type or mutant MC2R. Functional characterization of mutant MC2R was performed using a cell surface expression assay, a cAMP reporter assay, confocal microscopy and co-immunoprecipitation of MRAPα. Two thirds of all MC2R mutations had a significant reduction in cell surface trafficking even though MRAPα interacted with all mutants. Analysis of those mutant receptors that reached the cell surface indicated that 4/6 failed to signal, following stimulation with ACTH. The majority of MC2R mutations found in FGD fail to function because they fail to traffic to the cell surface.
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影响因子：
--
作者：
Conn, P Michael;Leanos-Miranda, Alfredo;Janovick, Jo Ann
通讯作者：
Janovick, Jo Ann
影响因子：
5.8
作者：
Janovick, JA;Maya-Nunez, G;Conn, PM
通讯作者：
Conn, PM
影响因子：
56.9
作者：
MOUNTJOY, KG;ROBBINS, LS;CONE, RD
通讯作者：
CONE, RD
DOI：
10.1001/archpedi.1959.02070010156002
发表时间：
1959-01-01
期刊：
AMA JOURNAL OF DISEASES OF CHILDREN
影响因子：
--
作者：
SHEPARD, TH;LANDING, BH;MASON, DG
通讯作者：
MASON, DG
影响因子：
4.8
作者：
Acharya, S;Karnik, SS
通讯作者：
Karnik, SS