Silencing GFAP isoforms in astrocytoma cells disturbs laminin-dependent motility and cell adhesion

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Moeton M, Kanski R, Stassen OMJA, Sluijs JA, Geerts D, van Tijn P, Wiche G, van Strien ME, Hol EM
Publisher: FEDERATION AMER SOC EXP BIOL
Publication year: 2014
Journal: FASEB Journal
Journal acronym: FASEB J
Volume number: 28
Issue number: 7
Start page: 2942
End page: 2954
Number of pages: 13
ISSN: 0892-6638


Abstract

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in astrocytes and neural stem cells. The GFAP gene is alternatively spliced, and expression of GFAP is highly regulated during development, on brain damage, and in neurodegenerative diseases. GFAP alpha is the canonical splice variant and is expressed in all GFAP-positive cells. In the human brain, the alternatively spliced transcript GFAP alpha marks specialized astrocyte populations, such as subpial astrocytes and the neurogenic astrocytes in the human subventricular zone. We here show that shifting the GFAP isoform ratio in favor of GFAP alpha in astrocytoma cells, by selectively silencing the canonical isoform GFAP alpha with short hairpin RNAs, induced a change in integrins, a decrease in plectin, and an increase in expression of the extracellular matrix component laminin. Together, this did not affect cell proliferation but resulted in a significantly decreased motility of astrocytoma cells. In contrast, a downregulation of all GFAP isoforms led to less cell spreading, increased integrin expression, and a >100-fold difference in the adhesion of astrocytoma cells to laminin. In summary, isoform-specific silencing of GFAP revealed distinct roles of a specialized GFAP network in regulating the interaction of astrocytoma cells with the extracellular matrix through laminin.


Keywords

glia, glioma, intermediate filaments

Last updated on 2019-23-09 at 04:35