Toro Carlos A, Eger Stephanie, Veliz Luis, Sotelo-Hitschfeld Pamela, Cabezas Deny, Castro Maite A, Zimmermann Katharina, Brauchi Sebastian
Instituto de Fisiología, Facultad de Medicina, Escuela de Graduados, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
Klinik für Anästhesiologie, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany, and Institut für Physiologie und Pathophysiologie, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
J Neurosci. 2015 Jan 14;35(2):571-82. doi: 10.1523/JNEUROSCI.3820-13.2015.
The spatial and temporal distribution of receptors constitutes an important mechanism for controlling the magnitude of cellular responses. Several members of the transient receptor potential (TRP) ion channel family can regulate their function by modulating their expression at the plasma membrane (PM) through rapid vesicular translocation and fusion. The mechanisms underlying this regulation are not completely understood, and the contribution of vesicular trafficking to physiological function is unknown. TRPM8 receptors are expressed in mammalian peripheral sensory neurons and are essential for the detection of cold temperatures. Previously, we showed that TRPM8-containing vesicles are segregated into three main pools, immobile at the PM, simple diffusive and corralled-hopping. Here, we show that channel expression at the PM is modulated by TRPM8 agonists in F11 and HEK293T cells. Our results support a model in which the activation of TRPM8 channels, located at the PM, induces a short-lived recruitment of a TRPM8-containing vesicular pool to the cell surface causing a transitory increase in the number of functional channels, affecting intrinsic properties of cold receptor responses. We further demonstrate the requirement of intact vesicular trafficking to support sustained cold responses in the skin of mice.
受体的时空分布是控制细胞反应强度的重要机制。瞬时受体电位（TRP）离子通道家族的几个成员可以通过快速囊泡转运和融合来调节其在质膜（PM）上的表达，从而调控自身功能。这种调节作用背后的机制尚未完全明确，囊泡运输对生理功能的贡献也不清楚。TRPM8受体在哺乳动物外周感觉神经元中表达，对冷觉检测至关重要。此前，我们发现含有TRPM8的囊泡可分为三个主要池，在质膜上静止不动、简单扩散和围栏跳跃。在此，我们表明在F11和HEK293T细胞中，TRPM8激动剂可调节质膜上的通道表达。我们的结果支持一种模型，即位于质膜上的TRPM8通道激活后，会诱导含TRPM8的囊泡池短暂募集到细胞表面，导致功能性通道数量短暂增加，影响冷感受器反应的内在特性。我们进一步证明，完整的囊泡运输是支持小鼠皮肤持续冷反应所必需的。
