Membrane targeting and interaction of NHE1 and NCX1 with integrinaIIbb3 by lipid microdomain induce a calcium influx that triggers calcium oscillation

• Main Authors: Yung-Hsiang Yi, 易永祥
• Other Authors: Chi-Hung Lin
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/p73e33

博士 === 國立陽明大學 === 微生物及免疫學研究所 === 97 === Abstract The cyclic calcium release-and-uptake during calcium oscillation is thought to result from calcium-induced calcium release (CICR); however, it is unclear, especially in non-excitable cells, how the initial calcium mobilization occurs that triggers CICR. We report here a novel mechanism, other than conventional calcium channels or phospholipase C-inositol trisphosphate system, for initiating calcium oscillation downstream of integrin signaling. Upon integrinαIIbβ3’s binding to fibrinogen ligand or the disintegrin rhodostomin, sodium-proton exchanger NHE1 and sodium-calcium exchanger NCX1 are actively transported to the plasma membrane and they become physically coupled to integrinαIIbβ3. Lipid raft-dependent mechanisms modulate the membrane targeting and formation of NHE1/integrinαIIbβ3/NCX1 protein complex. NHE1 and NCX1 within such protein complex are functionally coupled, such that a local increase of sodium concentration caused by NHE1 can drive NCX1 to generate sodium efflux in exchange for calcium influx. The resulting calcium increase inside the cell can then trigger CICR, as a prelude to calcium oscillation downstream of integrinαIIbβ3 signaling. Fluorescence resonance energy transfer based on fluorescence lifetime measurements is employed here to monitor the intermolecular interactions among NHE1/integrinαIIbβ3/NCX1, which could not be properly detected using conventional biochemical assays.