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

Abstract

Abstract. 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 EMimmunocytochemical 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 affinitypurified 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.variety of neurodegenerative diseases are known to be associated with different types of cancer, even though the tumor and its metastases have not invaded the nervous system (Brain and Norris, 1965;Brain and Wilkinson, 1965;

Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: Two ways to promote multifunctionality

“…The best characterized NCS protein is recoverin, a calcium-myristoyl switch protein in retinal rod cells (68,69) that controls desensitization of rhodopsin (33) by regulating rhodopsin kinase activity (70). Recoverin was also identified as the antigen in cancer-associated retinopathy (71). Other NCS proteins include neurocalcin (72), frequenin (NCS-1) (73), K ϩ channel-interacting proteins (KChIPs) (34), DREAM͞calsenilin (35,36) and hippocalcin (74).…”

Cancer-Associated Retinopathy during Treatment for Small-Cell Lung Carcinoma.

“…Thirkill et al (4) reported on the isolation of an autoantibody which reacts strongly the 23-kDa retinal protein, recoverin. This protein is a member of the E-F hand family of calcium-binding proteins involved in the transduction of light by vertebrate photoreceptors and is also identified as an autoantigen in CAR (12,13). It has been reported that this photoreceptor-specific protein is expressed by the tumor in CARpatients (16) and by a human lung cancer cell line (MN-1112), which was established from tumors of small-cell lung carcinoma patients with CAR (17,26).…”

“…CAR is associated with epithelial neoplasm, mostly small-cell lung carcinoma and is characterized by the degeneration of retinal photoreceptors (2-1 1). A photoreceptor protein, recoverin, has been recognized as the autoantigen of this disorder (12)(13)(14)(15)(16)(17). It has been reported that CARis usually found before the diagnosis of primary cancer, but there have been some reports that this disorder occurred during the treatment of malignant diseases (9,18,19).…”

Expression of a photoreceptor protein, recoverin, as a cancer-associated retinopathy autoantigen in human lung cancer cell lines

“…While the mechanism for paraneoplastic degenerative retinopathy has not been fully elucidated, the presence of peculiar antibodies in patients who suffer from this disease suggests that autoimmunity plays an important pathogenic role in the development of CAR (Thirkill et al, 1989(Thirkill et al, , 1993. Recently, the CAR antigen was identified as a 23 kDa photoreceptor protein, recoverin, from the screening of retinal proteins in CAR patients' sera (Polans et al, 1991;Thirkill et al, 1992). Recoverin is specifically localised in the photoreceptor cells and participates in the recovery phase of visual excitation and in adaptation to background light (Kawamura, 1994).…”