Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Adv Exp Med Biol. 2011;704:239-75. doi: 10.1007/978-94-007-0265-3_14.
TRPV5 and TRPV6 are unique members of the TRP super family. They are highly selective for Ca(2+) ions with multiple layers of Ca(2+)-dependent inactivation mechanisms, expressed at the apical membrane of Ca(2+) transporting epithelia, and robustly responsive to 1,25-dihydroxivitamin D(3). These features are well suited for their roles as Ca(2+) entry channels in the first step of transcellular Ca(2+) transport pathways, which are involved in intestinal absorption, renal reabsorption of Ca(2+), placental transfer of Ca(2+) to fetus, and many other processes. While TRPV6 is more broadly expressed in a variety of tissues such as esophagus, stomach, small intestine, colon, kidney, placenta, pancreas, prostate, uterus, salivary gland, and sweat gland, TRPV5 expression is relatively restricted to the distal convoluted tubule and connecting tubule of the kidney. There is only one TRPV6-like gene in fish and birds in comparison to both TRPV5 and TRPV6 genes in mammals, indicating TRPV5 gene was likely generated from duplication of TRPV6 gene during the evolution of mammals to meet the needs of complex renal function. TRPV5 and TRPV6 are subjected to vigorous regulations under physiological, pathological, and therapeutic conditions. The elevated TRPV6 level in malignant tumors such as prostate and breast cancers makes it a potential therapeutic target. TRPV6, and to a lesser extent TRPV5, exhibit unusually high levels of single nucleotide polymorphisms (SNPs) in African populations as compared to other populations, indicating TRPV6 gene was under selective pressure during or after humans migrated out of Africa. The SNPs of TRPV6 and TRPV5 likely contribute to the Ca(2+) conservation mechanisms in African populations.
TRPV5 和 TRPV6 是 TRP 超家族的独特成员。它们对 Ca(2+) 离子具有高度选择性，具有多层 Ca(2+)-依赖性失活机制，表达于 Ca(2+)转运上皮的顶端膜，并且对 1,25-二羟维生素 D(3) 反应强烈。这些特征非常适合它们作为 Ca(2+)进入通道的作用，在细胞间 Ca(2+)转运途径的第一步中，这些通道参与肠道吸收、Ca(2+)在肾脏的重吸收、胎盘向胎儿转移 Ca(2+)以及许多其他过程。虽然 TRPV6 在多种组织中广泛表达，如食管、胃、小肠、结肠、肾脏、胎盘、胰腺、前列腺、子宫、唾液腺和汗腺，但 TRPV5 的表达相对局限于肾脏的远曲小管和连接小管。鱼类和鸟类只有一个 TRPV6 样基因，而哺乳动物则有 TRPV5 和 TRPV6 两个基因，这表明 TRPV5 基因可能是在哺乳动物进化过程中从 TRPV6 基因复制而来的，以满足复杂肾功能的需要。TRPV5 和 TRPV6 在生理、病理和治疗条件下受到强烈的调节。在前列腺癌和乳腺癌等恶性肿瘤中，TRPV6 水平升高，使其成为一个潜在的治疗靶点。与其他人群相比，非洲人群中 TRPV6 基因的单核苷酸多态性 (SNP) 水平异常高，表明 TRPV6 基因在人类离开非洲后或在离开非洲的过程中受到了选择压力。TRPV6 和 TRPV5 的 SNPs 可能有助于非洲人群中的 Ca(2+) 保护机制。
