Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes.
Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes.
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DOI：
10.1111/pcmr.12083
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发表时间：
2013-05
影响因子：
4.3
通讯作者：
Setaluri V
中科院分区：
文献类型：
--
作者：
Devi S;Markandeya Y;Maddodi N;Dhingra A;Vardi N;Balijepalli RC;Setaluri V
TRPM1（一种在视网膜双极细胞和表皮黑素细胞中表达的钙通道）的突变会导致完全先天性静止性夜盲症，没有可辨别的皮肤表型。在视网膜中，TRPM1 活性通过 Gαo 与代谢型谷氨酸受体 6 (mGluR6) 信号传导负耦合，TRPM1 突变导致 TRPM1 对 mGluR6 信号传导的反应性丧失。在这里，我们表明人类黑素细胞表达 mGluR6，并且用 L-AP4（一种 III 型 mGluR 选择性激动剂）处理黑素细胞可增强 Ca2+ 吸收。通过 shRNA 敲低 TRPM1 或 mGluR6 可消除 L-AP4 诱导的 Ca2+ 内流和 TRPM1 电流，表明黑素细胞中的 TRPM1 活性与 mGluR6 信号传导正相关。黑素细胞中不存在 Gαo 蛋白。然而，Gαo 的强制表达恢复了 TRPM1 与 mGluR6 信号传导的负耦合，但用 Gi/Go 蛋白抑制剂百日咳毒素治疗并不影响基础或 mGluR6 诱导的 Ca2+ 摄取。此外，mGluR6 的慢性刺激改变了黑素细胞的形态并增加了黑色素含量。这些数据表明 TRPM1 功能与 mGluR6 信号传导耦合的差异解释了视网膜和皮肤中对谷氨酸的不同细胞反应。
Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6 and treatment of melanocytes with L-AP4, a type III mGluR-selective agonist, enhances Ca2+ uptake. Knockdown of TRPM1 or mGluR6 by shRNA abolished L-AP4-induced Ca2+ influx and TRPM1 currents showing that TRPM1 activity in melanocytes is positively coupled to mGluR6 signaling. Gαo protein is absent in melanocytes. However, forced expression of Gαo restored negative coupling of TRPM1 to mGluR6 signaling, but treatment with and pertussis toxin, an inhibitor of Gi/Go proteins, did not affect basal or mGluR6-induced Ca2+ uptake. Additionally, chronic stimulation of mGluR6 altered melanocyte morphology and increased melanin content. These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin.
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DOI：
10.1146/annurev.pharmtox.011008.145533
发表时间：
2010
影响因子：
12.5
作者：
Niswender CM;Conn PJ
通讯作者：
Conn PJ
DOI：
10.1523/jneurosci.1436-12.2012
发表时间：
2012-08-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dhingra A;Ramakrishnan H;Neinstein A;Fina ME;Xu Y;Li J;Chung DC;Lyubarsky A;Vardi N
通讯作者：
Vardi N
影响因子：
64.8
作者：
BREITWIESER, GE;SZABO, G
通讯作者：
SZABO, G
影响因子：
5.3
作者：
Dhingra, A;Jiang, MS;Vardi, N
通讯作者：
Vardi, N
DOI：
10.1111/j.1600-0749.2005.00284.x
发表时间：
2006-02-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Hoogduijn, MJ;Hitchcock, IS;Genever, PG
通讯作者：
Genever, PG