ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium.
ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium.
复制标题
DOI：
10.3389/fncel.2018.00071
复制
发表时间：
2018
影响因子：
5.3
通讯作者：
Lin W
中科院分区：
文献类型：
--
作者：
Fu Z;Ogura T;Luo W;Lin W
主要嗅觉上皮（MOE）的功能是检测气味分子，提供上皮表面屏障，并从吸入的空气中去除外来生物。在MOE内协调不同细胞类型的活动以维持这些功能的机制尚不清楚。在此之前，我们发现位于MOE表面的微绒毛细胞（MCs）表达瞬时受体电位通道M5 （TRPM5）具有胆碱能和化学反应性，它们在挑战性化学环境下维持气味反应和嗅觉引导行为中发挥重要作用。在这里，我们研究了TRPM5-MC的激活和随后的旁分泌调节。Ca2+成像显示，TRPM5-MCs在响应ATP（气道黏毛运动的重要信号分子）和气味混合物时，剂量依赖性地增加了细胞内Ca2+水平。药理检查表明ATP反应主要由P2X嘌呤能受体介导。有趣的是，使用内吞染料pHrodo红葡聚糖，我们发现与没有刺激的对照和对ATP或气味混合物没有反应的细胞相比，化学激活的TRPM5-MCs显著增加了pHrodo标记点的数量。这些结果表明，在释放信号分子乙酰胆碱（ACh）后，可能存在囊泡循环。有趣的是，TRPM5敲除（KO）导致atp诱导的pHrodo内化减少。我们进一步研究了邻近支持细胞（SCs）的胆碱能调节。我们发现乙酰胆碱能强烈地提高细胞内Ca2+并增强SCs中的pHrodo内吞作用。在阿托品或M3毒蕈碱受体拮抗剂存在和缺乏M3受体的SCs中，乙酰胆碱的作用减弱。总的来说，这些数据表明TRPM5-MCs可能通过胆碱能旁分泌信号调节MOE的多细胞网络活动，以维持功能和适应可塑性。
The main olfactory epithelium (MOE) functions to detect odor molecules, provide an epithelial surface barrier, and remove xenobiotics from inhaled air. Mechanisms coordinating the activities of different cell types within the MOE to maintain these functions are poorly understood. Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential channel M5 (TRPM5) are cholinergic and chemoresponsive and that they play an important role in maintaining odor responses and olfactory-guided behavior under challenging chemical environment. Here we investigated TRPM5-MC activation and subsequent paracrine regulation. Ca2+ imaging showed that TRPM5-MCs dose-dependently increase their intracellular Ca2+ levels in response to ATP, an important signaling molecule for airway mucociliary movement, and to an odor mixture. Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. Interestingly, using the endocytosis dye pHrodo Red dextran, we found that chemical-activated TRPM5-MCs significantly increase the number of pHrodo-labeled puncta compared to controls without stimulation and compared to cells that do not respond to ATP or to the odor mixture. These results indicate potential vesicle recycling after release of the signaling molecule acetylcholine (ACh). Interestingly, TRPM5 knockout (KO) results in a decrease in ATP-induced pHrodo internalization. We further investigated cholinergic regulation of neighboring supporting cells (SCs). We found that ACh strongly elevates intracellular Ca2+ and potentiates pHrodo endocytosis in SCs. The ACh effects are diminished in the presence of atropine or M3 muscarinic receptor antagonist and in SCs lacking M3 receptors. Collectively, these data suggest that TRPM5-MCs may regulate the MOE’s multicellular network activity via cholinergic paracrine signaling for functional maintenance and adaptive plasticity.
登录
查看更多内容
影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
影响因子：
2.5
作者：
Bezencon, C.;Fuerholz, A.;Damak, S.
通讯作者：
Damak, S.
DOI：
10.1073/pnas.1402436111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Deckmann, Klaus;Filipski, Katharina;Kummer, Wolfgang
通讯作者：
Kummer, Wolfgang
DOI：
10.3410/b3-20
发表时间：
2011
期刊：
F1000 biology reports
影响因子：
--
作者：
Finger TE;Kinnamon SC
通讯作者：
Kinnamon SC
影响因子：
3.7
作者：
Boase S;Foreman A;Cleland E;Tan L;Melton-Kreft R;Pant H;Hu FZ;Ehrlich GD;Wormald PJ
通讯作者：
Wormald PJ