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.
Roelofs
Reinko F
RF
Netherlands Institute for Brain Research, Graduate School Neurosciences, Amsterdam, the Netherlands.
Fischer
David F
DF
Houtman
Simone H
SH
Sluijs
Jacqueline A
JA
Van Haren
Wendy
W
Van Leeuwen
Fred W
FW
Hol
Elly M
EM
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