The SLC24 Na+/Ca2+-K+ exchanger family:: vision and beyond
The SLC24 Na+/Ca2+-K+ exchanger family:: vision and beyond
复制标题
DOI：
10.1007/s00424-003-1069-0
复制
发表时间：
2004-02-01
影响因子：
4.5
通讯作者：
Schnetkamp, PPM
中科院分区：
文献类型：
--
作者：
Schnetkamp, PPM
Na+/Ca 2 +-K+交换（NCKX）最早发现于脊椎动物视杆细胞（ROS）的外节，它是将通过光敏和cGMP门控通道进入ROS的Ca 2+挤出的唯一机制。ROS NCKX 1是唯一被广泛原位研究的NCKX基因家族成员。ROS NCKX 1 cDNA随后从包括人在内的许多物种中克隆，并显示为新基因家族（SLCA 24）的第一个成员。通过与NCKX 1同源性，随后克隆了人NCKX基因家族的另外三个成员（NCKX 2 -4），而第五个人NCKX基因的部分序列已出现在数据库中。NCKX相关基因也在低等动物中被发现，包括果蝇、蠕虫和海胆。NCKX 2在脑、视网膜锥光感受器和视网膜神经节细胞中表达，而NCKX 3和NCKX 4显示更广泛的表达模式。原位NCKX 1和异源表达的NCKX 2以4 Na（+）：1Ca（2+）+1 K+化学计量比运行; NCKX 1和NCKX 2都是双向转运蛋白，通常从细胞中挤出Ca 2+（正向交换），但当跨膜Na+梯度逆转时，也能够将Ca 2+携带到细胞中（反向交换）。在视网膜疾病患者中观察到NCKX 1和NCKX 2的序列变化，但尚未显示与视网膜疾病的明确关联。
Na+/Ca2+-K+ exchange (NCKX) was first discovered in the outer segments of vertebrate rod photoreceptors (ROS), where it is the only mechanism for extruding the Ca2+ that enters ROS via the light-sensitive and cGMP-gated channels. ROS NCKX1 is the only NCKX gene family member studied extensively in situ. ROS NCKX1 cDNAs have been cloned subsequently from a number of species including man and shown to be the first member of a new gene family (SLCA24). Three further members of the human NCKX gene family have been cloned subsequently (NCKX2-4) by homology with NCKX1, while a partial sequence of a fifth human NCKX gene has appeared in the data base. NCKX-related genes have also been identified in lower animals including fruit flies, worms and sea urchins. NCKX2 is expressed in the brain, in retinal cone photoreceptors and in retinal ganglion cells, while NCKX3 and NCKX4 show a broader expression pattern. In situ NCKX1 and heterologously expressed NCKX2 operate at a 4Na(+):1Ca(2+)+1 K+ stoichiometry; both NCKX1 and NCKX2 are bidirectional transporters normally extruding Ca2+ from the cell (forward exchange), but also able to carry Ca2+ into the cell (reverse exchange) when the transmembrane Na+ gradient is reversed. Sequence changes have been observed for both NCKX1 and NCKX2 in patients with retinal diseases, but a definitive association with retinal disease has not been shown.