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Publication : 14-3-3gamma affects dynamics and integrity of glial filaments by binding to phosphorylated GFAP.

First Author  Li H Year  2006
Journal  J Cell Sci Volume  119
Issue  Pt 21 Pages  4452-61
PubMed ID  17032734 Mgi Jnum  J:116069
Mgi Id  MGI:3692817 Doi  10.1242/jcs.03219
Citation  Li H, et al. (2006) 14-3-3gamma affects dynamics and integrity of glial filaments by binding to phosphorylated GFAP. J Cell Sci 119(Pt 21):4452-61
abstractText  Recent findings indicated a protective role of GFAP in ischemic brain, injured spinal cord, and in neurodegenerative disease. We previously demonstrated that 14-3-3gamma, once thought to be neuronal specific, was up-regulated by ischemia in astrocytes and may play a specific protective role in astrocytes. Here we report that 14-3-3gamma associates with both soluble and filamentous GFAP in a phosphorylation- and cell-cycle-dependent manner in primary cultured astrocytes. The amount of association increases during G2/M phase due to more phosphorylated GFAP. Moreover, this interaction is independent of vimentin, another type III intermediate filament protein in astrocytes which forms glial filaments with GFAP. A series of domain deletion mutants and substitution mutations at phosphorylation sites (from serine to alanine) on GFAP demonstrated that serine 8 in the head domain is essential for the direct association of GFAP to 14-3-3gamma. Overexpression of 14-3-3gamma destroyed the integrity and affected the movement of GFAP intermediate filaments. This data demonstrates that 14-3-3gamma contributes to the regulation of dynamics of GFAP filaments, which may contribute to the stability of the cytoskeleton and the mechanisms of central nervous system neurodegenerative disease.
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