Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy

Arthur S. Polans, Danuta Witkowska, Tammie L. Haley, Drake Amundson, Lawrence Baizer, Grazyna Adamus

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Recoverin is a member of the EF-hand family of calcium-binding proteins involved in the transduction of light by vertebrate photoreceptors. Recoverin also was identified as an autoantigen in the degenerative disease of the retina known as cancer-associated retinopathy (CAR), a paraneoplastic syndrome whereby immunological events lead to the degeneration of photoreceptors in some individuals with cancer. In this study, we demonstrate that recoverin is expressed in the lung tumor of a CAR patient but not in similar tumors obtained from individuals without the associated retinopathy. Recoverin was identified initially by Western blot analysis of the CAR patient's biopsy tissue by using antirecoverin antibodies generated against different regions of the recoverin molecule. In addition, cultured cells from the biopsy tissue expressed recoverin, as demonstrated by reverse transcription-PCR using RNA extracted from the cells. The immunodominant region of recoverin also was determined in this study by a solid-phase immunoassay employing overlapping heptapeptides encompassing the entire recoverin sequence. Two linear stretches of amino acids (residues 64-70, Lys- Ala-Tyr-Ala-Gln-His-Val; and 48-52, Gln-Phe-Gln-Ser-Ile) made up the major determinants. One of the same regions of the recoverin molecule (residues 64- 70) also was uniquely immunopathogenic, causing photoreceptor degeneration upon immunization of Lewis rats with the corresponding peptide. These data demonstrate that the neural antigen recoverin more than likely is responsible for the immunological events associated with vision loss in some patients with cancer. These data also establish CAR as one of the few autoimmune- mediated diseases for which the specific self-antigen is known.

Original languageEnglish (US)
Pages (from-to)9176-9180
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number20
DOIs
StatePublished - Sep 26 1995

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Ocular Paraneoplastic Syndromes
Recoverin
Calcium-Binding Proteins
Neoplasms
Autoantigens
EF Hand Motifs
Biopsy
Paraneoplastic Syndromes
Immunodominant Epitopes
Vertebrate Photoreceptor Cells
Immunoassay
Autoimmune Diseases
Reverse Transcription
Retina
Cultured Cells
Immunization

ASJC Scopus subject areas

  • Genetics
  • General

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Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy. / Polans, Arthur S.; Witkowska, Danuta; Haley, Tammie L.; Amundson, Drake; Baizer, Lawrence; Adamus, Grazyna.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 20, 26.09.1995, p. 9176-9180.

Research output: Contribution to journalArticle

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