Department of Internal Medicine, Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8856, USA.
Pflugers Arch. 2011 Aug;462(2):185-93. doi: 10.1007/s00424-011-0950-5. Epub 2011 Mar 29.
Klotho which was originally identified as an anti-aging protein is emerging as a substance with multiple effects on many systems including mineral homeostasis. In addition to its membrane-bound function as a co-receptor for fibroblast growth factor-23, soluble Klotho exerts effects as a circulating substance in plasma and urine. Novel features of this system include its autocrine-paracrine-endocrine glycan-modifying enzymatic function in the urinary lumen on calcium and phosphate transporters. Klotho induces phosphaturia by inhibiting the proximal tubule Na-coupled phosphate transporter. The action of Klotho is enzymatic in nature which includes alteration of transport activity and the more traditional means of regulation by trafficking. Klotho reduces calciuria by its distal as a sialidase directly on the apical calcium channel. Desialidation of the channel exposes glycan residues that promote binding to galectin-1, resulting in stabilization of residence on the plasma membrane. Through its systematic as well as renal actions, Klotho is emerging as a principal calciophosphoregulatory hormone.
Klotho 最初被鉴定为一种抗衰老蛋白，现在正成为一种在许多系统中具有多种作用的物质，包括矿物质稳态。除了作为成纤维细胞生长因子 23 的膜结合受体的功能外，可溶性 Klotho 还作为血浆和尿液中的循环物质发挥作用。该系统的新特征包括其在尿腔中的自分泌-旁分泌-内分泌糖修饰酶功能对钙和磷酸盐转运体的影响。Klotho 通过抑制近端小管 Na 偶联磷酸盐转运体来诱导磷酸盐尿。Klotho 的作用本质上是酶促的，包括改变转运活性和通过运输进行更传统的调节方式。Klotho 通过其在顶端钙通道上的唾液酸酶直接作为远端物质来减少钙尿。通道的去唾液酸化暴露了糖基残基，促进与半乳糖凝集素-1 的结合，从而稳定驻留在质膜上。通过其系统和肾脏作用，Klotho 正在成为一种主要的钙磷调节激素。
