Study on the tissue specific expression of phosphatidylinositol synthase and its function.

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Phosphatidylinositol synthase (PIS) catalyzes the formation of phosphatidylinositol (Pl) from myo-inositol and CDP-diacylglyceol and mediates the final step in the biosynthetic sequence leading to phosphoinositide. We have recently isolated and characterized a PIS cDNA from rat brain. The results obtained by this project are follows :i) In situ hybridization histochemistry revealed that PIS mRNA is selectively expressed in neuron-rich regions of the adult rat brain, such as cerebral cortex, hippocampus, thalamus, hypothalamus, and spinal cord. By contrast, little to no hybridization signal was observed in white matter-rich areas such as the corpus callosum. The expression of PIS mRNA was determinated during pre- and postnatal development of the rat central nervous system. On embryonic day 18, PIS was expressed mainly neuron-enriched areas such as cortical plate and ventricular zone whereas little to no mRNA is detected in glia-enriched areas.ii) Quantitative reverse transcription-polymerase chain reaction analysis as well as in situ hybridization showed that the PIS transcript level dramatically increased during the first postnatal week, and peaked at 7-14 days after birth.iii) Since the preliminary results suggested the presence of a new isoform of PIS, I tried to clone the isoform with several methods. But the new clone could not be isolated.iv) Dr. Umezawa(Keio Univ.) reported that inostamycin, known as a specific inhibitor of Pl synthesis, blocked both the Pl synthesis and G1 progression in the serum stimulated rat fibroblast cells. The collaboration study with him revealed that another inhibitor, delta- hexachlorocyclohexane, also blocked the both activity as inostamycin. Furthermore the blockade was due to the inhibition of the expression cyclin D and cyclin E.These results suggest that P13 plays an important role in cell cycle.