Cygnar Katherine D, Zhao Haiqing
Department of Biology, the Johns Hopkins University, Baltimore, Maryland, USA.
Nat Neurosci. 2009 Apr;12(4):454-62. doi: 10.1038/nn.2289. Epub 2009 Mar 22.
In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia has long been thought to account for rapid response termination by degrading odor-induced cAMP. Two PDEs with distinct cellular localization have been found in OSNs: PDE1C in the cilia and PDE4A throughout the cell but absent from the cilia. We disrupted both of these genes in mice and carried out electro-olfactogram analysis. Unexpectedly, eliminating PDE1C did not prolong response termination. Prolonged termination occurred only in mice that lacked both PDEs, suggesting that cAMP degradation by PDE1C in cilia is not a rate-limiting factor for response termination in wild-type mice. Pde1c(-/-) OSNs instead showed reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation. Our observations provide new perspectives on the regulation of olfactory transduction.
在鼻腔中，嗅觉感受器神经元（OSN）的纤毛上可检测到气味分子，在这里，一种由环磷酸腺苷（cAMP）介导的信号通路将气味刺激转化为电反应。长期以来，人们一直认为OSN纤毛中的磷酸二酯酶（PDE）活性通过降解气味诱导产生的cAMP来促使反应迅速终止。在OSN中发现了两种细胞定位不同的PDE：纤毛中的PDE1C以及遍布整个细胞但不存在于纤毛中的PDE4A。我们使小鼠体内的这两个基因均失活，并进行了电嗅觉图分析。出乎意料的是，去除PDE1C并没有延长反应终止时间。只有在同时缺失这两种PDE的小鼠中才出现了反应终止时间延长的情况，这表明纤毛中的PDE1C对cAMP的降解并非野生型小鼠反应终止的限速因素。相反，Pde1c基因敲除的OSN表现出敏感性降低以及对重复刺激的适应性减弱，这表明PDE1C可能参与调节敏感性和适应性。我们的观察结果为嗅觉转导的调节提供了新的视角。
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