Identification and characterization of GFAPκ, a novel glial fibrillary acidic protein isoform

Abstract

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, GFAPκ, produced by alternative splicing and polyadenylation of the 3′-region of the human GFAP pre-mRNA. As a consequence, the resulting human GFAPκ protein harbors a nonconserved C-terminal tail sequence distinct from the tails of GFAPα, the predominant GFAP isoform, and GFAPε, an isoform which also results from alternative splicing. The head and coiled-coil rod domains are identical between the three GFAP isoforms. Interestingly, GFAPκ is incapable of forming homomeric filaments, and increasing GFAPκ expression levels causes a collapse of intermediate filaments formed by GFAPα. In searching for a biological relevance of GFAPκ, we noticed that mRNA expression levels of GFAPα, GFAPε, and GFAPκ are gradually increased during development of the embryonic pig brain. However, whereas the GFAPα/GFAPε ratio is constant, the GFAPκ/GFAPε ratio decreases during brain development. Furthermore, in glioblastoma tumors, an increased GFAPκ/GFAPε ratio is detected. Our results suggest that the relative expression level of the GFAPκ 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. ©2007 Wiley-Liss, Inc.