title: Evolution of sialic acid-binding proteins: molecular cloning and expression of fish siglec-4.
abstract: Siglecs are the largest family of sialic acid-recognizing lectins identified so far with 11 members in the human genome. Most of these siglecs are exclusively expressed by cells of the immune system. Comparison of different mammalian species has revealed differential and complex evolutionary paths for this protein family, even within the primate lineage. To understand the evolution of siglecs, in particular the origin of this family, we investigated the occurrence of corresponding genes in bony fish. Interestingly, only unambiguous orthologs of mammalian siglec-4, a cell adhesion molecule expressed exclusively in the nervous system, could be identified in the genomes of fugu and zebrafish, whereas no obvious orthologs of the other mammalian siglecs were found. As in mammals, fish siglec-4 expression is restricted to nervous tissues as demonstrated by northern blot. Expressed as recombinant protein, fish siglec-4 binds to sialic acids with a specificity similar to the mammalian orthologs. Relatively low sequence similarities in the cytoplasmic tail as well as an additional splice variant found in fish siglec-4 suggest alternative signaling pathways compared to mammalian species. Our observations suggest that this siglec occurs at least in the nervous system of all vertebrates.
authors.affiliation: Centre for Biomolecular Interactions Bremen, Department of Biology and Chemistry, University Bremen, 28334 Bremen, Germany. flehmann@uni-bremen.de
authors.forename: Friederike
authors.initials: F
authors.lastname: Lehmann
authors.forename: Heiko
authors.initials: H
authors.lastname: Gäthje
authors.forename: Sørge
authors.initials: S
authors.lastname: Kelm
authors.forename: Frank
authors.initials: F
authors.lastname: Dietz
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007438:Introns / Q000235:genetics; D037102:Lectins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011485:Protein Binding; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013379:Substrate Specificity; D023741:Takifugu / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D029941:Fish Proteins; D037102:Lectins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019158:N-Acetylneuraminic Acid