A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.

A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.
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DOI:
10.1083/jcb.112.5.981
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发表时间:
1991-03
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Palczewski K
Palczewski K
中科院分区:
其他
文献类型:
--
作者:
Polans AS;Buczyłko J;Crabb J;Palczewski K

文献摘要

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癌症相关性视网膜病变(CAR)是一种副肿瘤综合征,其特征在于在肿瘤及其转移未侵入眼睛的情况下视网膜光感受器的变性。视网膜病变通常在癌症诊断之前就很明显,并且可能与与视网膜中特定部位反应的自身抗体有关。我们已经检查了来自CAR患者的血清以进一步表征视网膜抗原。人视网膜蛋白的Western印迹分析揭示了由CAR抗血清标记的26 kD处的突出条带。从复合CAR抗血清中亲和纯化26-kD蛋白的抗体,并用于蛋白质至视杆细胞和视锥细胞的细胞核、内节和外节的EM免疫细胞化学定位。从CAR血清获得的其他抗体不标记光感受器。使用亲和纯化的抗体进行检测,26-kD的蛋白质,命名为p26,纯化到均匀的从牛视杆细胞的外节通过苯基琼脂糖凝胶和离子交换色谱。p26的部分氨基酸序列通过气相Edman降解测定,并显示与视锥细胞特异性蛋白visinin具有广泛的同源性。基于结构相关性,p26杆蛋白和visinin都是钙调蛋白家族的成员,并且含有E-F手结构的钙结合结构域。
Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized by the degeneration of retinal photoreceptors under conditions where the tumor and its metastases have not invaded the eye. The retinopathy often is apparent before the diagnosis of cancer and may be associated with autoantibodies that react with specific sites in the retina. We have examined the sera from patients with CAR to further characterize the retinal antigen. Western blot analysis of human retinal proteins reveals a prominent band at 26 kD that is labeled by the CAR antisera. Antibodies to the 26-kD protein were affinity- purified from complex CAR antisera and used for EM-immunocytochemical localization of the protein to the nuclei, inner and outer segments of both rod and cone cells. Other antibodies obtained from the CAR sera did not label photoreceptors. Using the affinity-purified antibodies for detection, the 26-kD protein, designated p26, was purified to homogeneity from the outer segments of bovine rod photoreceptor cells by Phenyl-Sepharose and ion exchange chromatography. Partial amino acid sequence of p26 was determined by gas phase Edman degradation and revealed extensive homology with a cone-specific protein, visinin. Based upon structural relatedness, both the p26 rod protein and visinin are members of the calmodulin family and contain calcium binding domains of the E-F hand structure.