New GFAP splice isoform (GFAPμ) differentially expressed in glioma translates into 21 kDa N-terminal GFAP protein

The glial fibrillary acidic protein (GFAP) is a type III intermediate filament (IF) protein that is highly expressed in astrocytes, neural stem cells, and in gliomas. Gliomas are a heterogeneous group of primary brain tumors that arise from glia cells or neural stem cells and rely on accurate diagnosis for prognosis and treatment strategies. GFAP is differentially expressed between glioma subtypes and, therefore, often used as a diagnostic marker. However, GFAP is highly regulated by the process of alternative splicing; many different isoforms have been identified. Differential expression of GFAP isoforms between glioma subtypes suggests that GFAP isoform-specific analyses could benefit diagnostics. In this study we report on the differential expression of a new GFAP isoform between glioma subtypes, GFAP mu. A short GFAP transcript resulting from GFAP exon 2 skipping was detected by RNA sequencing of human glioma. We show that GFAP mu mRNA is expressed in healthy brain tissue, glioma cell lines, and primary glioma cells and that it translates into a similar to 21 kDa GFAP protein. 21 kDa GFAP protein was detected in the IF protein fraction isolated from human spinal cord as well. We further show that induced GFAFP mu expression disrupts the GFAP IF network. The characterization of this new GFAP isoform adds on to the numerous previously identified GFAP splice isoforms. It emphasizes the importance of studying the contribution of IF splice variants to specialized functions of the IF network and to glioma research.

Automated summary

GFAP is a highly expressed protein in astrocytes, neural stem cells, and gliomas, and is used as a diagnostic marker due to its differential expression between glioma subtypes. The discovery of a new GFAP isoform, GFAP mu, adds to the complexity of GFAP regulation and highlights the importance of studying IF splice variants for glioma research.