Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters.
Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters.
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DOI：
10.1016/j.celrep.2017.11.083
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发表时间：
2017-12-19
期刊：
影响因子：
8.8
通讯作者：
Gracheva EO
中科院分区：
文献类型：
--
作者：
Matos-Cruz V;Schneider ER;Mastrotto M;Merriman DK;Bagriantsev SN;Gracheva EO
13只衬里的地面松鼠和叙利亚仓鼠以其在冬眠期间抵御寒冷的能力而闻名。我们发现，冬眠者即使在活动状态下也表现出耐寒能力。对松鼠体感神经元的成像和电生理学研究表明，表达TRPM8的细胞对冷的敏感性降低。对松鼠和仓鼠TRPM8的表征表明，这些通道是化学激活的，但在冷条件下表现出较差的激活。通过转移冷敏感大鼠同源基因的跨膜结构域，可以将冷敏感基因重新引入松鼠和仓鼠的TRPM8。在松鼠TRPM8中，只需突变六种氨基酸就可以达到同样的效果。相互突变抑制了大鼠同源基因的冷敏感性，支持了这些残基的功能意义。我们的结果表明，沙鼠和仓鼠表现出较低的冷敏感度，部分原因是TRPM8跨膜区的修饰。我们的研究揭示了两种哺乳动物冬眠者伴随着耐寒性的分子适应。
Thirteen-lined ground squirrels and Syrian hamsters are known for their ability to withstand cold during hibernation. We found that hibernators exhibit cold tolerance even in the active state. Imaging and electrophysiology of squirrel somatosensory neurons reveal a decrease in cold sensitivity of TRPM8-expressing cells. Characterization of squirrel and hamster TRPM8 showed that the channels are chemically-activated, but exhibit poor activation by cold. Cold sensitivity can be re-introduced into squirrel and hamster TRPM8 by transferring the transmembrane domain from the cold sensitive rat orthologue. The same can be achieved in squirrel TRPM8 by mutating only six amino acids. Reciprocal mutations suppress cold sensitivity of the rat orthologue, supporting functional significance of these residues. Our results suggest that ground squirrels and hamsters exhibit reduced cold sensitivity partially due to modifications in the transmembrane domain of TRPM8. Our study reveals molecular adaptations that accompany cold tolerance in two species of mammalian hibernators.
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DOI：
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发表时间：
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期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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发表时间：
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影响因子：
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作者：
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