Rhythmic Trafficking of TRPV2 in the Suprachiasmatic Nucleus is Regulated by Prokineticin 2 Signaling.
Rhythmic Trafficking of TRPV2 in the Suprachiasmatic Nucleus is Regulated by Prokineticin 2 Signaling.
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DOI：
10.5334/jcr.ad
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发表时间：
2015-04-01
影响因子：
--
通讯作者：
Zhou QY
中科院分区：
文献类型：
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作者：
Burton KJ;Li X;Li JD;Hu WP;Zhou QY
哺乳动物的生物钟由单细胞振荡器组成。这些振荡器之间的神经化学和电信号传导对于昼夜节律的正常表达非常重要。动力蛋白 2 (PK2) 编码富含半胱氨酸的分泌蛋白，已被证明是调节昼夜节律的关键信号分子。视交叉上核 (SCN) 中的 PK2 表达具有高度节律性，在白天达到峰值，在夜间基本不表达。 PK2 基因或其受体 PKR2 被破坏的小鼠表现出广泛的昼夜节律参数（例如运动活动、体温和睡眠/觉醒模式）的节律性大大降低。 PK2 已被证明可以增加 SCN 神经元的放电率，但分子机制尚不清楚。在这里，我们报道TRPV2是一种属于TRP家族的离子通道，在SCN神经元中与PKR2共表达。此外，TRPV2 蛋白（而非 TRPV2 mRNA）被证明以 PK2 依赖性方式在 SCN 中振荡。功能研究表明，TRPV2 可能通过增加 TRPV2 向细胞表面的运输来增强 PKR2 在钙动员或离子电流电导方面的信号传导。综上所述，这些结果表明 TRPV2 可能是昼夜节律调节中 PK2 下游信号传导的一部分。
The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms.