Yarovinsky T O, Rickman D W, Diamond R H, Taub R, Hageman G S, Bowes Rickman C
Department of Ophthalmology and Visual Sciences, University of Iowa College of Medicine, 200 Hawkins Blvd., Iowa City, IA, USA.
Brain Res Mol Brain Res. 2000 Apr 14;77(1):95-103. doi: 10.1016/s0169-328x(00)00045-0.
Foveal cone photoreceptors are morphologically distinct and, presumably, express unique transcripts. We have identified a cDNA clone encoding the protein tyrosine phosphatase (PTP), phosphatase of regenerating liver 1 (PRL-1) in a screen for genes that are enriched in monkey fovea. PRL-1 was originally isolated as an immediate early gene in regenerating liver [R.H. Diamond, D.E. Cressman, T.M. Laz, C.S. Abrams, R. Taub, PRL-1, a unique nuclear protein tyrosine phosphatase, affects cell growth, Mol. Cell Biol. 14 (1994) 3752-3762]. On cDNA Southern blots of human and monkey retina, radiolabeled PRL-1 cDNA hybridized to a single mRNA species of about 2.5 kb that was most intense in fovea-enriched samples. The monkey PRL-1 deduced amino acid sequence is identical to human, rat and mouse PRL-1. Affinity-purified antibodies directed against PRL-1 preferentially labeled cone photoreceptor cells and a subpopulation of bipolar cells in monkey retina. Immunoreactivity in cones was confined to red and green, but not to blue, cones and was restricted to the outer segments. Immunolocalization also revealed that PRL-1 protein expression was non-nuclear, suggesting that its function in the retina may be unrelated to its role in other tissues where it is expressed primarily in nuclei. Although both foveal and extrafoveal cones were PRL-1 reactive, the high abundance of PRL-1 mRNAs detected in monkey fovea correlates with the high concentration of cones in the fovea. The PRL-1 gene is located on chromosome 6q within an interval that also contains the genes that cause two hereditary retinal dystrophies. These studies demonstrate novel expression of the PRL-1 gene in the neural retina and suggest the phosphatase activity of PRL-1 may modulate normal cone photoreceptor cell function.
中央凹视锥光感受器在形态上是独特的,并且推测表达独特的转录本。我们在筛选富集于猴中央凹的基因时,鉴定出一个编码蛋白酪氨酸磷酸酶(PTP)——再生肝脏1磷酸酶(PRL-1)的cDNA克隆。PRL-1最初是作为再生肝脏中的一个立即早期基因被分离出来的[R.H. 戴蒙德,D.E. 克雷斯曼,T.M. 拉兹,C.S. 艾布拉姆斯,R. 陶布,PRL-1,一种独特的核蛋白酪氨酸磷酸酶,影响细胞生长,《分子细胞生物学》14(1994)3752 - 3762]。在人和猴视网膜的cDNA Southern杂交印迹上,放射性标记的PRL-1 cDNA与一种约2.5 kb的单一mRNA杂交,该mRNA在富含中央凹的样本中最为强烈。推导的猴PRL-1氨基酸序列与人、大鼠和小鼠的PRL-1相同。针对PRL-1的亲和纯化抗体优先标记猴视网膜中的视锥光感受器细胞和双极细胞亚群。视锥细胞中的免疫反应性局限于红锥和绿锥,而不包括蓝锥,并且局限于外段。免疫定位还显示PRL-1蛋白表达不在细胞核中,这表明其在视网膜中的功能可能与其在其他主要在细胞核中表达的组织中的作用无关。尽管中央凹和中央凹外的视锥细胞都有PRL-1反应性,但在猴中央凹中检测到的高丰度PRL-1 mRNA与中央凹中视锥细胞的高浓度相关。PRL-1基因位于6号染色体q臂上的一个区间内,该区间还包含导致两种遗传性视网膜营养不良的基因。这些研究证明了PRL-1基因在神经视网膜中的新表达,并表明PRL-1的磷酸酶活性可能调节正常视锥光感受器细胞的功能。