Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

Abstract

The present review describes recent research on the regulation by glutamate and Ca 2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca 2+ . The lack of external Ca 2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca 2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca 2+ -dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca 2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca 2+ entry into the astrocytes and consequently down-regulates a Ca 2+ -dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation state of GFAP and a consequent increase in the number of mitotic astrocytes.

Laminar and subcellular heterogeneity of GLAST and GLT‐1 immunoreactivity in the developing postnatal mouse hippocampus

“…GFAP not only controls astrocytic motility and shape by providing structural stability (Rodnight et al, 1997), Figure 9. Clusters of GLT-1 at GFAP-labeled astrocyte endfeet.…”

Neuromuscular activity impairs axonal sprouting in partially denervated muscles by inhibiting bridge formation of perisynaptic Schwann cells

“…Perisynaptic Schwann cells express muscarinic acetylcholine receptors that normally respond to acetylcholine released from the active nerve terminals, leading to influx of calcium, which in turn down-regulates glial fibrillary acidic protein (GFAP) (Jahromi et al, 1992;Rodnight et al, 1997;Rochon et al, 2001;Georgiou et al, 1999). The down-regulation of GFAP has been linked directly to the lack of processes of perisynaptic Schwann cells in normally innervated muscles (Rodnight et al, 1997;Rochon et al, 2001;Georgiou et al, 1999). Accordingly, upon partial denervation, the perisynaptic Schwann cells at denervated endplates that are no longer exposed to acetylcholine up-regulate GFAP and extend processes.…”

Multiple Retinol and Retinal Dehydrogenases Catalyze All-trans-retinoic Acid Biosynthesis in Astrocytes

“…Astrocyte purity was assessed by assaying for expression of GFAP, an astrocyte marker (57). Immunostaining showed that Ͼ98% of the cultured cells were GFAP positive (Fig.…”