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hMRAPa 增加 αMSH 诱导的 hMC1R 和 hMC3R 功能偶联和 hMC4R 组成型活性。

hMRAPa increases αMSH-induced hMC1R and hMC3R functional coupling and hMC4R constitutive activity.

机构信息

Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.

出版信息

J Mol Endocrinol. 2013 Feb 26;50(2):203-15. doi: 10.1530/JME-12-0221. Print 2013 Apr.

DOI:10.1530/JME-12-0221
PMID:23296982
Abstract

Human melanocortin 2 receptor accessory protein (hMRAPa) is hypothesised to have functions beyond promoting human melanocortin 2 receptor (hMC2R) functional expression. To understand these potential functions, we exogenously co-expressed hMRAPa-FLAG with each of the five hMCR subtypes in HEK293 cells and assessed hMCR subtype coupling to adenylyl cyclase. We also co-expressed each HA-hMCR subtype with hMRAPa-FLAG to investigate their subcellular localisation. hMRAPa-FLAG enhanced α-melanocyte stimulating hormone (α-MSH)-stimulated hMC1R and hMC3R but reduced NDP-α-MSH-stimulated hMC5R, maximum coupling to adenylyl cyclase. hMRAPa-FLAG specifically increased hMC4R constitutive coupling to adenylyl cyclase despite not co-localising with the HA-hMC4R in the cell membrane. hMRAPa-FLAG co-localised with HA-hMC1R or HA-hMC3R in the perinuclear region, in cytoplasmic vesicles and at the plasma membrane, while it co-localised with HA-hMC2R, HA-hMC4R and HA-hMC5R predominantly in cytoplasmic vesicles. These diverse effects of hMRAPa indicate that hMRAPa could be an important modulator of the central and peripheral melanocortin systems if hMRAPa and any hMCR subtype co-express in the same cell.

摘要

人黑素皮质素 2 受体辅助蛋白（hMRAPa）被假设具有促进人黑素皮质素 2 受体（hMC2R）功能表达以外的功能。为了理解这些潜在的功能，我们在外源共表达 hMRAPa-FLAG 与 HEK293 细胞中的五种 hMCR 亚型中的每一种，并评估 hMCR 亚型与腺苷酸环化酶的偶联。我们还共表达了每个 HA-hMCR 亚型与 hMRAPa-FLAG，以研究它们的亚细胞定位。hMRAPa-FLAG 增强了 α-促黑素细胞刺激素（α-MSH）刺激的 hMC1R 和 hMC3R，但降低了 NDP-α-MSH 刺激的 hMC5R，最大程度地与腺苷酸环化酶偶联。hMRAPa-FLAG 特异性增加了 hMC4R 的组成性与腺苷酸环化酶的偶联，尽管它不在细胞膜上与 HA-hMC4R 共定位。hMRAPa-FLAG 与 HA-hMC1R 或 HA-hMC3R 在核周区、细胞质小泡和质膜中共定位，而与 HA-hMC2R、HA-hMC4R 和 HA-hMC5R 主要在细胞质小泡中共定位。hMRAPa 的这些不同作用表明，如果 hMRAPa 和任何 hMCR 亚型在同一细胞中共表达，hMRAPa 可能是中枢和外周黑素皮质素系统的重要调节剂。

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