Structural and functional characterization of the zebrafish gene for glial fibrillary acidic protein, GFAP.
Glial fibrillary acidic protein, GFAP, is an astrocyte-specific member of the family of intermediate filament proteins which are involved in formation of the cytoskeletal structure. We here present a characterization of the zebrafish GFAP gene and corresponding protein. The zebrafish GFAP gene have the same exon-intron organization as the mammalian orthologoue genes. Comparison of the protein with mammalian GFAP shows that the amino acid sequence is highly conserved in the rod and tail domains whereas the head domain has diverged. Zebrafish GFAP exhibits functional characteristics of an intermediate filament protein such as dimerization potential, capacity to assembly into filaments, and cytoskeletal localization. Mutations in human GFAP have been associated with a severe childhood brain disorder called Alexander disease. Interestingly, the mutations affect preferentially amino acid residues of GFAP that are evolutionarily conserved. This indicates that a change of functionally core residues in GFAP is a prerequisite for the disease phenotype to develop and the initial steps in the pathogenesis may thus be modeled in zebrafish.
Nielsen
Anders Lade
AL
Department of Human Genetics, The Bartholin Building, University of Aarhus, DK-8000, Aarhus C, Denmark. aln@humgen.au.dk
Jørgensen
Arne Lund
AL
D038261:Alexander Disease / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D019143:Evolution, Molecular; D005091:Exons; D005796:Genes / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D049452:Green Fluorescent Proteins; D049669:History, 16th Century; D006801:Humans; D007382:Intermediate Filaments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007438:Introns; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D015027:Zebrafish / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004247:DNA