Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes.
Anti-CV2 autoantibodies have recently been discovered in patients with paraneoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti-CV2 autoantibodies recognize a brain protein of 66 kDa developmentally regulated and specifically expressed by a subpopulation of oligodendrocytes in the adult brain. Here, we demonstrate that anti-CV2 sera recognize several post-translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous to the Unc-33 gene product in Caenorhabditis elegans. The sequence of the human Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2-q26, a region mutated in glioblastomas and containing tumour suppressor genes. The identification of the Ulip/CRMP proteins as recognized by anti-CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendrocytes and into pathophysiology of PND.
Honnorat
J
J
INSERM U 433, Hôpital Neurologique, Lyon, France. honnorat@cismsun.univ-lyon1.fr
Byk
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Kusters
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Aguera
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Ricard
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Rogemond
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Quach
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Aunis
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Sobel
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Mattei
M G
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Kolattukudy
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Belin
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Antoine
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D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D020361:Paraneoplastic Syndromes, Nervous System / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D001323:Autoantibodies; D018076:DNA, Complementary; C102926:DPYSL3 protein, human; D000939:Epitopes; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins