Study on physiological function of brain-specific PNP 14

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PNP 14 is a family protein of synucleini, which is recently thought to be responsible for Alzheimer's and Parkinson's diseases. In the present study, age-dependent changes in the expression lebel of PNP 14 in the rat brain was examined by using specific antibody and nucleotide probes. The expression of mRNA for PNP 14 was investigated by in situ hybridization and found abundantly in olfactory bulb, hippocampus, and cerebellar cortex when juvenile rats were used. Expression level of the mRNA decreased with increasing age. Although the very low expression in the brain of rat embryo was detected by Northern blot analysis, it significantly increased in that of adult rat. Immunoblot analysis of PNP 14 in the brain indicated that decrease in protein levels of PNP 14 was also found in an age-dependent manner in the same regions except in the olfactory bulb. The decrease in protein levels in the brain appears to be due to decrease in expression of the mRNA.It is thought that physiological function of PNP 14 in the rat brain might be diminished in an age-dependent manner.It was determined that l27Tyrosine residue of PNP 14 was phosphorylated in vitro bytyrosine kinases such as EGF receptors and src-kinase. Synucleini was also phosphorylated by both tyrosine kinases. These results are useful to clarify the physiological function of PNP 14 family proteins.It was shown that domain Ill of PNP 14 and a-synuclein is responsible for the binding to GAPDH.The amino acid sequence, KKE(D)X_<3-6>KXEE in domain III of both proteins may be important as target for GAPDH.Transgenic mice introducing the gene of PNP 14 and synucleini were produced. The phenotypic analysis will be investigated.