ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer
ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer
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DOI：
10.1016/j.bbrc.2007.12.153
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发表时间：
2008-03-07
影响因子：
3.1
通讯作者：
Sharma, Rameshwar K.
中科院分区：
文献类型：
--
作者：
Duda, Teresa;Sharma, Rameshwar K.
Ca2+调节的ONE-GC膜鸟苷酸环化酶是气味转导中环GMP信号的中心组成部分。它是一个单一的跨膜跨越模块蛋白。它的细胞内区域包含与GCAP1和神经钙素δ相关的Ca2+传感器识别域，以及催化模块。这些结构域感知游离Ca2+的增量并刺激催化模块。本研究在机理上取得了三个重大进展。首先，到目前为止，还没有已知的细胞外结构域的配体，因此ONE-GC被认为是一个孤儿受体。本研究鉴定了其配体。乌观音通过其外域刺激ONE-GC。其次，到目前为止，还没有已知的配体可以直接刺激任何膜鸟苷酸环化酶的催化模块。目前的证据表明，在半微摩尔范围的游离Ca2+的存在下，神经钙素结合到催化模块并刺激ONE-GC。因此，one - gc具有三模式调节，两种发生在细胞内，一种发生在细胞外。第三，一种尿液气味剂观音林不会直接刺激ONE-GC。这挑战了先前提出的假设，即观音林气味信号是通过ONE-GC发生的[T]。陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强，陈志强。学会科学。美国。[104](2007) 14507 - 14512。(c) 2007爱思唯尔公司版权所有。
The Ca2+-modulated ONE-GC membrane guanylate cyclase is a central component of the cyclic GMP signaling in odorant transduction. It is a single transmembrane spanning modular protein. Its intracellular region contains Ca2+ sensor recognition domains linked to GCAP1 and to neurocalcin delta, and a catalytic module. These domains sense increments in free Ca2+ and stimulate the catalytic module. The present study makes three significant mechanistic advancements. First, to date no ligand for the extracellular (ext) domain is known, for this reason ONE-GC has been deemed as an orphan receptor. The present study identifies its ligand. Uroguanylin stimulates ONE-GC through its ext domain. Second, so far no ligand is known that directly stimulates the catalytic module of any membrane guanylate cyclase. The presented evidence shows that in the presence of the semimicromolar range of free Ca2+, neurocalcin binds to the catalytic module and stimulates ONE-GC. Thus, ONE-GC has trimodal regulation, two occurring intracellularly and one extracellularly. Third, guanylin, a urine odorant, does not directly stimulate ONE-GC. This challenges the proposed hypothesis that the guanylin odorant signal occurs via ONE-GC [T. Leinders-Zufall, R.E. Cockerham, S. Michalakis, M. Biel, D.L. Garbers, R.R. Reed, F. Zufall, S.D. Munger, Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium, Proc. Natl. Acad. Sci. USA. 104 (2007) 14507 - 14512]. (c) 2007 Elsevier Inc. All rights reserved.