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Ligand density dramatically affects integrin alpha IIb beta 3-mediated platelet signaling and spreading
Markéta Jirousková1, Jyoti K Jaiswal, Barry S Coller
1Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY 10021, USA. marketa@rockefeller.edu
Blood
|March 3, 2007
Summary
Ligand density significantly impacts integrin signaling. Low fibrinogen density promotes rapid calcium flux and cell spreading, while high density alters signaling pathways for different cellular responses.
Area of Science:
- Cellular Biology
- Biochemistry
- Biophysics
Background:
- Integrin-mediated cell adhesion and outside-in signaling are crucial cellular processes.
- The precise role of ligand density in modulating integrin function remains incompletely understood.
Purpose of the Study:
- To investigate how varying surface densities of fibrinogen influence alpha IIb beta3 integrin-mediated platelet adhesion and signaling.
- To elucidate the distinct signaling pathways activated by different fibrinogen densities.
Main Methods:
- Total internal reflection fluorescent microscopy
- Conformation-specific antibodies
- Calcium (Ca2+) flux measurements
Main Results:
- Surface density of fibrinogen differentially affects alpha IIb beta3-mediated platelet signaling, adhesion, and spreading.
- Low fibrinogen density triggers rapid cytosolic Ca2+ increases and sequential filopodia/lamellipodia formation.
- High fibrinogen density leads to transient/no Ca2+ increases and simultaneous filopodia/lamellipodia formation, with more dynamic receptor-ligand engagement.
Conclusions:
- Two distinct signaling mechanisms are initiated by alpha IIb beta3 integrin interacting with fibrinogen at different densities.
- Src/Rac activity and actin polymerization are key for low-density adhesion, while PKC/PI3 kinases are important for high-density spreading.
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