Identification and characterization of GFAPkappa, a novel glial fibrillary acidic protein isoform.
Glial fibrillary acidic protein (GFAP) is the principal component of the intermediary filaments in mature astrocytes of the central nervous system (CNS). The protein consists of three domains: the head, the coiled-coil, and the tail. Here, we describe the isolation of an evolutionary conserved novel GFAP isoform, GFAPkappa, produced by alternative splicing and polyadenylation of the 3'-region of the human GFAP pre-mRNA. As a consequence, the resulting human GFAPkappa protein harbors a nonconserved C-terminal tail sequence distinct from the tails of GFAPalpha, the predominant GFAP isoform, and GFAPepsilon, an isoform which also results from alternative splicing. The head and coiled-coil rod domains are identical between the three GFAP isoforms. Interestingly, GFAPkappa is incapable of forming homomeric filaments, and increasing GFAPkappa expression levels causes a collapse of intermediate filaments formed by GFAPalpha. In searching for a biological relevance of GFAPkappa, we noticed that mRNA expression levels of GFAPalpha, GFAPepsilon, and GFAPkappa are gradually increased during development of the embryonic pig brain. However, whereas the GFAPalpha/GFAPepsilon ratio is constant, the GFAPkappa/GFAPepsilon ratio decreases during brain development. Furthermore, in glioblastoma tumors, an increased GFAPkappa/GFAPepsilon ratio is detected. Our results suggest that the relative expression level of the GFAPkappa isoform could modulate the properties of GFAP intermediate filaments and perhaps thereby influencing the motility of GFAP positive astrocytes and progenitor cells within the CNS.
Blechingberg
Jenny
J
Institute of Human Genetics, The Bartholin Building, University of Aarhus, Aarhus C DK-8000, Denmark.
Holm
Ida Elisabeth
IE
Nielsen
Karsten Bork
KB
Jensen
Torben Heick
TH
Jørgensen
Arne Lund
AL
Nielsen
Anders Lade
AL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D017385:Sequence Homology
D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; D020033:Protein Isoforms; D012333:RNA, Messenger