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Compartmentalization regulates the interaction between the platelet integrin alpha IIb beta 3 and ICln
Deirdre Larkin1, Achim Treumann, Derek Murphy
1Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
British Journal of Haematology
|December 6, 2008
Summary
Platelet activation regulates the interaction between the volume-regulating protein ICln and integrin alpha(IIb)beta(3). ICln redistribution to the platelet membrane controls this interaction during activation.
Area of Science:
- Platelet biology
- Integrin signaling
- Protein-protein interactions
Background:
- ICln is a volume-regulating protein found in the platelet cytosol.
- Integrin alpha(IIb)beta(3) is associated with platelet membranes and cytoskeleton.
- The interaction between ICln and alpha(IIb)beta(3) is crucial for platelet function.
Purpose of the Study:
- To investigate the regulation of ICln and alpha(IIb)beta(3) interaction during platelet activation.
- To understand the role of subcellular localization in this interaction.
Main Methods:
- Used His-tagged recombinant ICln to study binding to purified and platelet-derived alpha(IIb)beta(3).
- Investigated binding under conditions of direct integrin activation and occupancy inhibition.
- Monitored ICln redistribution and integrin binding capacity over time during prolonged platelet activation.
Main Results:
- Recombinant ICln bound equally to purified alpha(IIb)beta(3) from resting or activated platelets.
- Binding was unaffected by direct integrin activation or occupancy inhibitors.
- Prolonged platelet activation led to a slow downregulation of ICln-integrin interaction capacity.
- ICln redistributed to membrane and cytoskeletal fractions preceding the downregulation of binding capacity.
Conclusions:
- ICln has the inherent capacity to bind alpha(IIb)beta(3) regardless of integrin activation state.
- Platelet activation is required for ICln to interact with alpha(IIb)beta(3).
- Activation-dependent subcellular redistribution of ICln provides a novel mechanism for temporally regulating integrin function in platelets.
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