Phosphorylation of adenylyl cyclase III at serine1076 does not attenuate olfactory response in mice.
Phosphorylation of adenylyl cyclase III at serine1076 does not attenuate olfactory response in mice.
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DOI：
10.1523/jneurosci.0559-12.2012
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发表时间：
2012-10-17
期刊：
影响因子：
--
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Cygnar KD;Collins SE;Ferguson CH;Bodkin-Clarke C;Zhao H
腺苷酸环化酶III（ACIII）通过钙离子诱导的磷酸化反馈抑制长期以来一直被认为有助于嗅觉感觉神经元（OSN）的反应终止和适应。为了直接确定这种反馈机制在体内嗅觉的功能意义，我们在小鼠中将ACIII的丝氨酸1076（负责Ca 2+诱导的磷酸化和抑制ACIII的唯一残基）遗传突变为丙氨酸。免疫组化和Western blot分析表明，突变既不影响纤毛定位，也不影响ACIII在OSN中的表达水平。嗅觉电图分析显示野生型和突变小鼠对单脉冲气味刺激或几种适应性刺激范式的反应没有差异。这些结果表明，丝氨酸1076上的ACIII磷酸化在嗅觉反应衰减中的作用远不如以前认为的重要。
Feedback inhibition of adenylyl cyclase III (ACIII) via Ca2+-induced phosphorylation has long been hypothesized to contribute to response termination and adaptation of olfactory sensory neurons (OSNs). To directly determine the functional significance of this feedback mechanism for olfaction in vivo, we genetically mutated serine1076 of ACIII, the only residue responsible for Ca2+-induced phosphorylation and inhibition of ACIII, to alanine in mice. Immunohistochemistry and Western blot analysis showed that the mutation affects neither the cilial localization nor the expression level of ACIII in OSNs. Electroolfactogram analysis showed no differences in the responses between wildtype and mutant mice to single-pulse odorant stimulations or in several stimulation paradigms for adaptation. These results suggest that phosphorylation of ACIII on serine1076 plays a far less important role in olfactory response attenuation than previously thought.