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Clathrin-mediated integrin αIIbβ3 trafficking controls platelet spreading
Wen Gao1, Panlai Shi2, Xue Chen2
1a Department of Cardiology , Huashan Hospital, Fudan University , Shanghai , China.
Platelets
|September 30, 2017
Summary
Integrin αIIbβ3 trafficking is crucial for platelet activation. Pitstop 2, a clathrin-mediated endocytosis inhibitor, disrupts this process, impacting platelet spreading and aggregation.
Area of Science:
- Cell Biology
- Hematology
- Biochemistry
Background:
- Integrin trafficking is vital for cell functions like migration and cytokinesis.
- Integrin αIIbβ3 is critical for thrombosis and hemostasis, but its trafficking role in platelet activation is unclear.
Purpose of the Study:
- To investigate the role of integrin αIIbβ3 endocytic and exocytic trafficking in platelet activation.
- To determine if clathrin-mediated endocytosis is involved in integrin αIIbβ3 trafficking during platelet activation.
Main Methods:
- Utilized pitstop 2, a selective inhibitor of clathrin-mediated endocytosis.
- Assessed human platelet spreading on fibrinogen.
- Investigated integrin αIIbβ3 and fibrinogen uptake and recycling.
- Analyzed the association of αIIbβ3 with clathrin and AP2.
- Examined the Src/PLC/PKC signaling pathway.
Main Results:
- Pitstop 2 inhibited human platelet spreading on fibrinogen.
- Pitstop 2 did not block αIIbβ3 and fibrinogen endocytosis but inhibited αIIbβ3 recycling.
- Pitstop 2 enhanced αIIbβ3 association with clathrin and AP2, suggesting disturbed dissociation.
- The Src/PLC/PKC pathway triggers αIIbβ3 endocytosis during platelet activation.
- Pitstop 2 inhibited platelet aggregation and secretion.
Conclusions:
- Integrin αIIbβ3 trafficking is clathrin-dependent and critical for platelet spreading.
- Pitstop 2 is a valuable tool for studying clathrin-mediated trafficking in platelets and may have therapeutic potential.
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