Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton.
Human glial fibrillary acidic protein-delta (GFAP-delta) is a GFAP protein isoform that is encoded by an alternative splice variant of the GFAP-gene. As a result, GFAP-delta protein differs from the predominant splice form, GFAP-alpha, by its C-terminal protein sequence. In this study, we show that GFAP-delta protein is not expressed by all GFAP-expressing astrocytes but specifically by a subpopulation located in the subpial zone of the cerebral cortex, the subgranular zone of the hippocampus, and, most intensely, by a ribbon of astrocytes following the ependymal layer of the cerebral ventricles. Therefore, at least in the sub ventricular zone (SVZ), GFAP-delta specifically marks the population of astrocytes that contain the neural stem cells in the adult human brain. Interestingly, the SVZ astrocytes actively splice GFAP-delta transcripts, in contrast to astrocytes adjacent to this layer. Furthermore, we show that GFAP-delta protein, unlike GFAP-alpha, is not upregulated in astrogliosis. Our data therefore indicate a different functional role for GFAP-delta in astrocyte physiology. Finally, transfection studies showed that GFAP-delta protein expression has a negative effect on GFAP filament formation, and therefore could be important for modulating intermediate filament cytoskeletal properties, possibly facilitating astrocyte motility. Further studies on GFAP-delta and the cells that express it are important for gaining insights into its function during differentiation, migration and during health and disease.
Netherlands Institute for Brain Research, Graduate School Neurosciences, Amsterdam, the Netherlands.
Reinko F
RF
Roelofs
David F
DF
Fischer
Simone H
SH
Houtman
Jacqueline A
JA
Sluijs
Wendy
W
Van Haren
Fred W
FW
Van Leeuwen
Elly M
EM
Hol
D017398:Alternative Splicing / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004805:Ependyma / Q000378:metabolism / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism* / Q000648:ultrastructure; D020547:Lateral Ventricles / Q000378:metabolism / Q000648:ultrastructure; D010841:Pia Mater / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger