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© Research
Publication : The Journal of neuroscience : the official journal of the Society for Neuroscience

Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of neuroscience : the official journal of the Society for Neuroscience - 15 Aug 2002

Takemura M, Gomi H, Colucci-Guyon E, Itohara S

Link to Pubmed [PMID] – 12177195

J. Neurosci. 2002 Aug;22(16):6972-9

Glial fibrillary acidic protein (GFAP), the principal intermediate filament (IF) protein of mature astrocytes in the CNS, plays specific roles in astrocyte functions. GFAP has multiple phosphorylation sites at its N-terminal head domain. To examine the role of phosphorylation at these sites, we generated a series of substitution mutant mice in which phosphorylation sites (Ser/Thr) were replaced by Ala, in different combinations. Gfap(hm3/hm3) mice carrying substitutions at all five phosphorylation sites showed extensive decrease in both filament formation and amounts of GFAP. Gfap(hm1/hm1) and Gfap(hm2/hm2) mice, which carry substitutions at three of five sites and in different combinations, showed differential phenotypes. Although Gfap(hm3/hm3) mice retained GFAP filaments in Bergmann glia in the cerebellum, the (Gfap(hm3/hm3):Vim(-/-)) mice lacked GFAP filaments. Pulse-chase experiments of cultured astrocytes indicated that the Hm3-GFAP encoded by Gfap(hm3) was unstable particularly in the absence of vimentin, another IF protein. These results revealed the role of phosphorylation in turnover of GFAP and a synergistic role of GFAP and vimentin in the dynamics of glial filaments. The data further suggest that each of the phosphorylated sites has a distinct impact on the dynamics of GFAP.

http://www.ncbi.nlm.nih.gov/pubmed/12177195