2007 Fiscal Year Final Research Report Summary
Molecular analysis of lipid rafts involved in T-cell acrivation
| Project/Area Number |
18570118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
IWASHITA Yoshiko Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolit, Senior Research Scientist (50111498)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Lipid raft / T lymphocyte / Signal transduction / Cell membrane / Cholesterol |
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| Research Abstract |
To study the molecular basis of lipid rafts involved in T-cell activation, we examined the alterations of lipid rafts in an age-associated decline in T-cell receptor signaling. By analyzing the effect of aging on the constituents of lipid rafts in resting mouse CD4^+ T cells, we found a pronounced, age-dependent reduction in PAG (a phosphoprotein associated with glycosphingolipid-enriched microdomains). PAG is involved in the regulation of Src family kinases(SFKs) by recruiting Csk (a negative regulator of SFKs) to lipid rafts. This reduction is specific for T cells and is attributed, at least in part, to the reduction in its mRNA level. The reduction of PAG accompanies marked impairment in recruiting Csk to lipid rafts, resulting in dysregulation of SFKs' activities. This defect in a negative SFK regulatory system may be related to the age-dependent decline in T-cell receptor signaling. Along with the above analyses, we developed a method to visualize cholesterol in cholesterol-rich microdomains in cultured cells. This method will be useful to monitor the dynamic behavior of lipid rafts during cell signaling.
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