Thursday, December 16, 20102:00 PM - 3:00 PMCNLS Conference Room (TA-3, Bldg 1690)|
Mechanistic model of lipid raft regulation of IgE receptor signaling
Dipak BaruaTheoretical Biology and Biophysics Group, LANL , CNLS
Lipid rafts are discrete regions in the plasma membrane enriched in cholesterol and spingolipids. They are thought to play an important role in IgE receptor signaling. The rafts preferentially localize the key IgE receptor signaling pro- teins inside the raft regions while exclude the phosphatases into the non-raft region of the membrane. Such raft-localization allegedly protects the proteins from dephosphorylation by phosphatases. This allows the proteins to remain phospohrylated and induce signaling for longer time periods. However, con- tradictory experimental data showing rapid dephosphorylation of raft-localized
proteins argues for no raft protection of phosphorylated proteins. Here, we aim to resolve the existing controversies and elucidate the actual mechanism of lipid raft function. Through our model analysis, we show that lipid rafts indeed protect signaling proteins from ephosphorylation. Our results indicate rapid dephosphorylation kinetics for aft-localized proteins even at strong levels of lipid raft protection. In addition, we show how the life-time of lipid rafts compromise their ability to protect protein phosphorylation. At life time less than a second, lipid rafts become incompetent to oer protection to phospho- rylated proteins. On the other hand, at life-times longer than 10 sec, protein dephosphorylation kinetics in the model deviates from experimental data. The model therefore reveals a life-time of 3 10 sec for any signal competent lipid raft in the plasma membrane.
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