A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.
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.
Polans
A S
AS
R. S. Dow Neurological Sciences Institute, Good Samaritan Hospital and Medical Center, Portland, Oregon 97209.
Buczyłko
J
J
Crabb
J
J
Palczewski
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D002417:Cattle; D002852:Chromatography, Ion Exchange; D005136:Eye Proteins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D007106:Immune Sera; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010257:Paraneoplastic Syndromes / Q000276:immunology / Q000378:metabolism*; D051603:Recoverin; D012160:Retina / Q000737:chemistry* / Q000276:immunology; D012162:Retinal Degeneration / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000737:chemistry / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D007106:Immune Sera; D009419:Nerve Tissue Proteins; C067574:RCV1 protein, Bos taurus; C045140:visinin; D051603:Recoverin