Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels
Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels
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DOI：
10.1073/pnas.1604269113
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发表时间：
2016-10-04
影响因子：
11.1
通讯作者：
Gracheva, Elena O.
中科院分区：
文献类型：
--
作者：
Laursen, Willem J.;Schneider, Eve R.;Gracheva, Elena O.
感知热量的能力对于生存至关重要。耐热性的提高可能是有益的，因为它赋予了栖息在原本令人望而却步的生态位的能力。这种现象很普遍，在大型和小型动物中都有发现。例如，地松鼠和骆驼比许多其他哺乳动物物种更能耐受 40 摄氏度以上的温度，但维持这种能力的分子机制尚不清楚。瞬时受体电位香草酸 1 (TRPV1) 是一种多模式离子通道，参与体感系统初级传入对有害热和化学刺激的检测。在这里，我们发现十三系地松鼠 (Ictidomys tridecemlineatus) 和双峰驼 (Camelus ferus) 表达 TRPV1 直向同源物，但温度敏感性显着降低。敏感性的丧失仅限于温度，并且不会影响辣椒素或酸反应，从而保持 TRPV1 作为有毒化学线索检测器的作用。我们表明，通过 N 端锚蛋白重复结构域中的单个氨基酸取代，可以在两个 TRPV1 直向同源物中重新设计热敏感性。相反，相互突变抑制大鼠 TRPV1 的热敏感性，支持残基的功能保护。我们的研究表明，松鼠和骆驼采用了一种共同的分子策略，通过抑制体感神经元水平上 TRPV1 介导的热检测效率来适应炎热环境。这种适应是可能的，因为TRPV1分子具有显着的功能灵活性，它可以以最小的单个氨基酸变化的成本进行深刻的调整。
The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 degrees C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by primary afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV1 orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV1 as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV1 orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV1, supporting functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV1-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV1 molecule, which can undergo profound tuning at theminimal cost of a single amino acid change.