Neurobiology Group, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste 34136, Italy.
Molecular Physiology of Somatic Sensation, Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin D-13122, Germany.
eNeuro. 2021 Mar 12;8(2). doi: 10.1523/ENEURO.0565-20.2021. Print 2021 Mar-Apr.
Stomatin-like protein-3 (STOML3) is an integral membrane protein expressed in the cilia of olfactory sensory neurons (OSNs), but its functional role in this cell type has never been addressed. STOML3 is also expressed in dorsal root ganglia neurons, where it has been shown to be required for normal touch sensation. Here, we extended previous results indicating that STOML3 is mainly expressed in the knob and proximal cilia of OSNs. We additionally showed that mice lacking STOML3 have a morphologically normal olfactory epithelium. Because of its presence in the cilia, together with known olfactory transduction components, we hypothesized that STOML3 could be involved in modulating odorant responses in OSNs. To investigate the functional role of STOML3, we performed loose patch recordings from wild-type (WT) and knock-out (KO) OSNs. We found that spontaneous mean firing activity was lower with additional shift in interspike intervals (ISIs) distributions in KOs compared with WT neurons. Moreover, the firing activity in response to stimuli was reduced both in spike number and duration in neurons lacking STOML3 compared with WT neurons. Control experiments suggested that the primary deficit in neurons lacking STOML3 was at the level of transduction and not at the level of action potential generation. We conclude that STOML3 has a physiological role in olfaction, being required for normal sensory encoding by OSNs.
质膜蛋白 3（STOML3）是一种表达在嗅觉感觉神经元（OSN）纤毛中的整合膜蛋白，但它在这种细胞类型中的功能作用尚未得到解决。STOML3也在背根神经节神经元中表达，在这些神经元中，它被证明是正常触觉所必需的。在这里，我们扩展了以前的结果，表明 STOML3 主要在 OSN 的小球和近端纤毛中表达。我们还表明，缺乏 STOML3 的小鼠具有形态正常的嗅上皮。由于其存在于纤毛中，以及已知的嗅觉转导成分，我们假设 STOML3 可能参与调节 OSN 对气味的反应。为了研究 STOML3 的功能作用，我们对野生型（WT）和敲除（KO）OSN 进行了松散贴片记录。我们发现，与 WT 神经元相比，KO 神经元中的自发平均放电活动较低，并且尖峰间间隔（ISI）分布进一步转移。此外，与 WT 神经元相比，缺乏 STOML3 的神经元对刺激的反应活性在尖峰数量和持续时间上均降低。对照实验表明，缺乏 STOML3 的神经元的主要缺陷是在转导水平而不是动作电位产生水平。我们得出结论，STOML3 在嗅觉中具有生理作用，是 OSN 正常感觉编码所必需的。
