Second messenger molecules have a limited spread in olfactory cilia.
Second messenger molecules have a limited spread in olfactory cilia.
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DOI：
10.1085/jgp.201812126
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发表时间：
2018-12-03
期刊：
影响因子：
--
通讯作者：
Kurahashi T
中科院分区：
文献类型：
--
作者：
Takeuchi H;Kurahashi T
嗅觉感受器细胞纤毛的嗅觉反应持续时间超过10 S，这不能用第二信使的自由扩散来解释。Takeuchi和Kurahashi表明，这些信号分子的传播范围有限，并在产生地点停留很长时间。气味是通过嗅觉受体细胞(ORCS)的感觉纤毛上的嗅觉受体来检测的。这些柱状纤毛的直径为100-200 nm，腺酰环化酶-cAMP系统信号转导所需的成分位于其中。气味反应的动力学由活性蛋白质的寿命以及第二信使分子(cAMP和Ca~(2+))的产生、扩散和挤出/降解决定。然而，关于ORC反应的分子动力学信息有限，主要是因为研究这种狭窄的空间和精细结构所涉及的技术限制。在这项研究中，结合电生理学、笼状物质的光解和斑点UV激光刺激，我们证明了第二信使分子只在嗅觉纤毛的产生部位附近起作用。这种有限的扩散清楚地解释了ORCS的一个独特特征，即它们在低钙条件下表现出的整数倍的么正事件。尽管小的ORC在细胞的不同区域使用cAMP和Ca~(2+)来实现各种功能，但这些物质似乎只在被适当刺激激活的隔室中起作用。我们还表明，这些物质在相同的附近停留了很长时间。这使得ORC能够放大气味信号，并延长依赖钙的适应的寿命。细胞质缓冲区和挤出/降解系统似乎在限制分子扩散方面起着至关重要的作用。此外，由于高表面积/体积比，质膜表面的结合部位可能会限制分子在如此狭窄的空间内的扩散。这种高效的能量转换也可以广泛应用于其他尚未进行系统实验的生物系统。
Olfactory responses in the cilia of olfactory receptor cells last for longer than 10 s, which cannot be explained by free diffusion of second messengers. Takeuchi and Kurahashi show that these signaling molecules have a limited spread and remain at the site of generation for a long time. Odorants are detected by olfactory receptors on the sensory cilia of olfactory receptor cells (ORCs). These cylindrical cilia have a diameters of 100–200 nm, within which the components required for signal transduction by the adenylyl cyclase–cAMP system are located. The kinetics of odorant responses are determined by the lifetimes of active proteins as well as the production, diffusion, and extrusion/degradation of second messenger molecules (cAMP and Ca2+). However, there is limited information about the molecular kinetics of ORC responses, mostly because of the technical limitations involved in studying such narrow spaces and fine structures. In this study, using a combination of electrophysiology, photolysis of caged substances, and spot UV laser stimulation, we show that second messenger molecules work only in the vicinity of their site of generation in the olfactory cilia. Such limited spreading clearly explains a unique feature of ORCs, namely, the integer multiple of unitary events that they display in low Ca2+ conditions. Although the small ORC uses cAMP and Ca2+ for various functions in different regions of the cell, these substances seem to operate only in the compartment that has been activated by the appropriate stimulus. We also show that these substances remain in the same vicinity for a long time. This enables the ORC to amplify the odorant signal and extend the lifetime of Ca2+-dependent adaptation. Cytoplasmic buffers and extrusion/degradation systems seem to play a crucial role in limiting molecular spreading. In addition, binding sites on the cytoplasmic surface of the plasma membrane may limit molecular diffusion in such a narrow space because of the high surface/volume ratio. Such efficient energy conversion may also be broadly used in other biological systems that have not yet been subjected to systematic experiments.
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