Headless splice variant acting as dominant negative calcitonin receptor
Headless splice variant acting as dominant negative calcitonin receptor
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DOI：
10.1016/j.bbrc.2007.08.107
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发表时间：
2007-11-03
影响因子：
3.1
通讯作者：
Hirose, Shigehisa
中科院分区：
文献类型：
--
作者：
Nag, Kakon;Sultana, Naznin;Hirose, Shigehisa
降钙素受体（CTR）是B类G蛋白偶联受体（GPCR）超家族成员。我们最近确定了CTR基因和它的两个转录异构体，mfCTR和mfCTR Δ N，在mefugu（MF）（东方鲀ohscurus）。在这里，我们表征了缺乏结合蛋白酶的胞外N-末端结构域的mfCTR Δ N。北方分析显示，其mRNA在肝脏中的强表达和弱但广泛的组织分布表明这种无头剪接变体的生理意义。生物化学和免疫细胞化学分析表明，它作为一个自然发生的显性负亚型形成异源二聚体与正常CTR。无头的mfCTR Δ N的特点是这里是第一例的N-末端截短的显性负性形式的GPCR，和免疫细胞化学用于检测异源二聚体的形成可能是有用的，作为一种新的方法，用于分析膜蛋白在活细胞中的相互作用。(C)2007爱思唯尔公司All rights reserved.
Calcitonin receptor (CTR) is a member of class B G protein-coupled receptor (GPCR) superfamily. We have recently identified the CTR gene and its two transcriptional isoforms, mfCTR and mfCTR Delta N, in mefugu (mf) (Takifugu ohscurus). Here we characterized the mfCTR Delta N that lacks hormone-binding extracellular N-terminal domain. Strong expression in the liver and weak but broad tissue distribution of its mRNA, revealed by Northern analysis, suggested physiological significance of this headless splice variant. Biochemical and immunocytochemical analyses revealed that it acts as a naturally occurring dominant negative isoform by forming a heterodimer with normal CTR. The headless mfCTR Delta N characterized here is the first case of N-terminally truncated dominant negative form of GPCR, and immunocytochemistry used for detecting the heterodimer formation may be useful as a novel method for analyzing membrane protein interaction in a living cell. (C) 2007 Elsevier Inc. All rights reserved.