TPPP/p25: from unfolded protein to misfolding disease: prediction and experiments

• DOI: 10.1016/j.biolcel.2004.08.002
• Publication Date: 2004-10-12T17:34:08Z
• Authors: F. Orosz; G.G. Kovács; A. Lehotzky; J. Oláh; O. Vincze; J. Ovádi
• Keywords: Triosephosphate isomerase; Glyceraldehyde 3-phosphate dehydrogenase

TPPP/p25, the first representative of a new protein family, identified as brain-specific unfolded induces aberrant microtubule assemblies in vitro, suppresses mitosis Drosophila embryo and is accumulated inclusion bodies human pathological brain tissues. In this paper, we present prediction additional experimental data that validate TPPP/p25 to be member "intrinsically unstructured" family. The comparison these characteristics with alpha-synuclein tau, involved also neurodegenerative diseases, suggested although primary sequences proteins are entirely different, there similarities their well-defined unstructured segments interrupted by "stabilization centres", phosphorylation tubulin binding motives. SK-N-MC neuroblastoma cells were transfected pEGFP-TPPP/p25 construct stable clone denoted K4 was selected used establish effect on energy state/metabolism cells. Our analyzing mitochondrial membrane polarization fluorescence microscopy revealed high-energy phosphate production not damaged expression. Biochemical analysis cell homogenates provided quantitative ATP level increased 1.5-fold activities hexokinase, glucosephosphate isomerase, phosphofructokinase, triosephosphate isomerase glyceraldehyde-3-phosphate dehydrogenase 1.2 2.0-fold higher compared control. modelling using rate equations individual enzymes suggests expression stimulates glucose metabolism. At conditions localized multiple system atrophy, it tightly co-localizes alpha-synuclein, partially vimentin. previous studies obtained immunohistochemistry tissues rendered possible classify among inclusions basis immunolabelling suggest potential linkage between Parkinson's Alzheimer's diseases.