Abstract
The present review describes recent research on the regulation by glutamate and Ca2+ 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 Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ 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 Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ 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.
Highlights
The mammalian brain contains two main groups of cells: the neurons and the neuroglia
The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices
Since group II metabotropic glutamate receptor (mGluR) do not act by liberating Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ entry into the astrocytes and down-regulates a Ca2+-dependent dephosphorylation cascade regulating the phosphorylation state of GFAP
Summary
The mammalian brain contains two main groups of cells: the neurons and the neuroglia. In this review we focus on factors regulating the phosphorylation state of glial fibrillary acidic protein (GFAP) in immature astrocytes. GFAP is a class III intermediate filament (IF) protein which exhibits dynamic properties similar to those of other members of this class of proteins These dynamic properties of GFAP are modulated by phosphorylation and play a fundamental role in astrocytic plasticity. S100ß, a Ca2+-binding protein expressed in astrocytes, may be involved in glial filament formation [49] Another interesting fact is that in immature or injured astrocytes GFAP can coassemble with vimentin, a process that is dependent on the KLLEGEE sequence mentioned above [44]. Filaments are assembled or incorporated into preformed filaments uniformly throughout the cytoplasm and an apparent polar or vectorial incorporation (from the perinuclear region to the cell periphery) may be the consequence of a nonuniform distribution of these filaments [50,51]
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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