The astrocytic cytoskeleton: Unravelling the role of GFAPδ

Abstract

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