A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway
A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway
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DOI：
10.1073/pnas.94.7.3388
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Beavo, JA
中科院分区：
文献类型：
--
作者：
Juilfs, DM;Fulle, HJ;Beavo, JA
气味信息是由一系列细胞内信号转导事件编码的，这些事件主要由第二信使cAMP介导。我们发现有一部分嗅觉神经元表达cGMP刺激的磷酸二酯酶（PDE2）和鸟酰环化酶- d (GC-D)，提示这些神经元中的cGMP在嗅觉信号传导中也有重要的调控功能，PDE2和GC-D都在嗅觉纤毛中表达，而PDE2仅在轴突中表达。与大多数其他嗅觉神经元相比，这些神经元似乎投射到嗅球中一个独特的肾小球组，类似于被称为“项链肾小球”的子集。此外，这一神经元子集的独特之处在于，它们不包含先前确定的涉及cAMP和钙的嗅觉信号转导级联的几个成分，包括钙/钙调素依赖性PDE （PDE1C2）、腺苷酸环化酶III和cAMP特异性PDE （PDE4A）。有趣的是，后三种蛋白在相同的神经元中表达：然而，它们的亚细胞分布是不同的。PDE1C2和腺苷酸环化酶III几乎只在嗅纤毛中表达，而PDE4A仅存在于细胞体和离子中。这些数据有力地表明，不同PDEs和环化酶的选择性区隔化是嗅觉神经元和其他神经元信号转导调节的重要特征，此外，这些数据表明，嗅神经上皮的一些神经元中存在由cGMP特异性调节的嗅觉信号转导途径。
Odorant information is encoded by a series of intracellular signal transduction events thought to be mediated primarily by the second messenger cAMP. We have found a subset of olfactory neurons that express the cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D (GC-D), suggesting that cGMP in these neurons also can have an important regulatory function in olfactory signaling, PDE2 and GC-D are both expressed in olfactory cilia where odorant signaling is initiated: however, only PDE2 is expressed in axons. In contrast to most other olfactory neurons, these neurons appear to project to a distinct group of glomeruli in the olfactory bulb that are similar to the subset that have been termed ''necklace glomeruli.'' Furthermore, this subset of neurons are unique in that they do not contain several of the previously identified components of olfactory signal transduction cascades involving cAMP and calcium, including a calcium/calmodulin-dependent PDE (PDE1C2), adenylyl cyclase III, and cAMP-specific PDE (PDE4A). Interestingly, these latter three proteins are expressed in the same neurons: however, their subcellular distribution is distinct. PDE1C2 and adenylyl cyclase III are expressed almost exclusively in the olfactory cilia whereas PDE4A is present only in the cell bodies and a?ions. These data strongly suggest that selective compartmentalization of different PDEs and cyclases is an important feature for the regulation of signal transduction in olfactory neurons and likely in other neurons as well, In addition, the data implies that an olfactory signal transduction pathway specifically modulated by cGMP is present in some neurons of the olfactory neuroepithelium.