| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
Disialic acid (diSia) is involved in neurite differentiation as well as T cell growth, and present on a few glycoproteins like CD166 in neural cells. CD166 is a cell adhesion molecule commonly occurring in mammalian brain and T lymphocytes ; however, a role of the diSia on CD166 remains unelucidated. The objective of this research project was to understand a regulatory mechanism of cell differentiation and growth by the diSia epitope. For this purpose, we have done the followings :
1.Molecular mechanism for stimulation of neurite formation by the diSia epitope :
In addition to CD166,a 130 kDa cadherin was identified as a diSia-containing glycoprotein. The diSia epitope is present on O-linked glycan(s) in cadherin, like CD166. The expression of at least two α2,8-sialyltransferases responsible for biosynthesis of the diSia were demonstrated. Moreover, the diSia epitope was accumulated in lipid rafts in budding sites of neurites in the beginning of neurite formation. It is thus suggested that the diSia epitope on CD166 and/or cadherin on the lipid rafts is functionally important.
2.Molecular mechanism for an antigen-independent T cell growth by the diSia epitope :
In mouse T cells, 100 kDa and 200 kDa glycoproteins were detected, and the 100 kDa-glycoprotein was demonstrated to be CD166. We also demonstrated that an antigen-independent T cell proliferation by the CD3/CD4-ligation was greatly enhanced by co-incubation with anti-diSia antibody. Under the conditions, the diSia epitope on both glycolipids and CD166 was increased, with a concomitant increase in expression of mRNAs for CD166,possibly involved α2,8-sialyltransferases. Furthermore, the diSia epitopes on the glycolipids and CD166 are enriched in lipid rafts, suggesting that they cooperatively operate to enhance the T-cell proliferation.
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