Glial fibrillary acidic protein (GFAP) is the main intermediate filament (IF) in astrocytes. The GFAP gene can give rise to
different splice isoforms, of which GFAPα is the canonical isoform. GFAPδ is an isoform which in the human SVZ is expressed
in specific astrocytes; the adult neural stem cells. Expression differences between these isoforms lead to the hypothesis
that GFAPδ may play a functional role in specific subtypes of astrocytes. In overexpression studies, we investigated the effects
of GFAP isoform expression on the IF network and functional features of neurogenic astrocytes. We confirmed that GFAPδ expression
collapses the GFAP network which altered cell morphology but not motility or proliferation rate. Since there is a constant
exchange of proteins from an insoluble form to soluble form in the cytoplasm we assessed the dynamic properties of GFAPα and
GFAPδ. The exchange rate of GFAPδ was lower compared to GFAPα and the exchange rates of both isoforms were decreased in a
collapsed IF network. A role for GFAPδ in both cell motility and cell adhesion was found in experiments where the endogenous
GFAP isoform levels were altered with specific isoform knockdown. Moreover, the expression levels of integrins, plectin and
Laminin1a were regulated in cells with a high GFAPδ:GFAPɑ ratio. The molecular mechanisms underlying the influence of GFAPδ
on cell motility, adhesion, and extracellular matrix (ECM) related protein expression is still unknown. Future research should
focus on the link between the IF network, the ECM, integrin signalling and the role of GFAPδ therein.
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