Identification and characterization of GFAP kappa 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, GFAP kappa, produced by alternative splicing and polyadenylation of the T-region of the human GFAP pre-mRNA. As a consequence, the resulting human GFAPK protein harbors a nonconserved C-terminal tail sequence distinct from the tails of GFAP alpha the predominant GFAP isoform, and GFAP epsilon, an isoform which also results from alternative splicing. The head and coiled-coil rod domains are identical between the three GFAP isoforms. Interestingly, GFAP kappa is incapable of forming homomeric filaments' and increasing GFAP kappa expression levels causes a collapse of intermediate filaments formed by GFAP alpha In searching for a biological relevance of GFAP kappa, we noticed that mRNA expression levels of GFAP alpha GFAP epsilon, and GFAPK are gradually increased during development of the embryonic pig brain. However, whereas the GFAP alpha/GFAP epsilon ratio is constant, the GFAP kappa/GFAP epsilon ratio decreases during brain development. Furthermore, in glioblastoma tumors, an increased GFAP kappa/GFAP epsilon ratio is detected. Our results suggest that the relative expression level of the GFAPK 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. (c) 2007 Wiley-Liss, Inc.