TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption
TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption
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DOI：
10.1007/978-3-642-54215-2_13
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Peng, Ji-Bin
中科院分区：
文献类型：
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作者：
Na, Tao;Peng, Ji-Bin
TRPV 5是TRPV家族中对Ca 2+离子表现出高选择性的两个通道之一。TRPV 5介导Ca 2+内流进入细胞，作为跨上皮转运Ca 2+的第一步。TRPV 5在肾脏远端小管中的专门分布使其成为Ca 2+重吸收的关键参与者。TRPV 5对激素如1，25-二羟基维生素D-3、甲状旁腺激素、雌激素和睾酮的表达和/或活性的响应性使得TRPV 5适合于其在Ca 2+重吸收的微调中的作用。通过调节TRPV 5的运输和活性，进一步优化了这种作用，所述TRPV 5的运输和活性通过其结合配偶体;共表达的蛋白质;管状因子，如钙结合蛋白-D-28 k、钙调蛋白、klotho、尿调蛋白和纤溶酶;细胞外和细胞内因子，如质子、Mg 2+、Ca 2+和磷脂酰肌醇-4，5-二磷酸;以及流体流动。这些调节允许TRPV 5调节其整体活性以响应身体对Ca 2+的需求并防止肾结石形成。小鼠Trpv 5基因的点突变导致类似于Trpv 5敲除小鼠的高钙尿症，表明TRPV 5在人类高钙尿症中的可能作用。此外，Trpv 5基因的单核苷酸多态性在非洲后裔中的存在可能有助于非洲后裔中有效的肾脏Ca 2+重吸收。TRPV 5代表了Ca 2+稳态改变疾病的潜在治疗靶点。
TRPV5 is one of the two channels in the TRPV family that exhibit high selectivity to Ca2+ ions. TRPV5 mediates Ca2+ influx into cells as the first step to transport Ca2+ across epithelia. The specialized distribution in the distal tubule of the kidney positions TRPV5 as a key player in Ca2+ reabsorption. The responsiveness in expression and/or activity of TRPV5 to hormones such as 1,25-dihydroxyvitamin D-3, parathyroid hormone, estrogen, and testosterone makes TRPV5 suitable for its role in the fine-tuning of Ca2+ reabsorption. This role is further optimized by the modulation of TRPV5 trafficking and activity via its binding partners; co-expressed proteins; tubular factors such as calbindin-D-28k, calmodulin, klotho, uromodulin, and plasmin; extracellular and intracellular factors such as proton, Mg2+, Ca2+, and phosphatidylinositol-4,5-bisphosphate; and fluid flow. These regulations allow TRPV5 to adjust its overall activity in response to the body's demand for Ca2+ and to prevent kidney stone formation. A point mutation in mouse Trpv5 gene leads to hypercalciuria similar to Trpv5 knockout mice, suggesting a possible role of TRPV5 in hypercalciuric disorders in humans. In addition, the single nucleotide polymorphisms in Trpv5 gene prevalently present in African descents may contribute to the efficient renal Ca2+ reabsorption among African descendants. TRPV5 represents a potential therapeutic target for disorders with altered Ca2+ homeostasis.