Document Type
Article
Publication Date
5-24-2017
Abstract
BACKGROUND: It is believed that activation of c-Src bound to the integrin β3 subunit initiates outside-in signaling. The involvement of αIIb in outside-in signaling is poorly understood.
OBJECTIVES: We have previously shown that CIB1 specifically interacts with the cytoplasmic domain of αIIb and is required for αIIbβ3 outside-in signaling. Here we evaluated the role of CIB1 in regulating outside-in signaling in the absence of inside-out signaling.
METHODS: We used αIIb cytoplasmic domain peptide and CIB1-function blocking antibody to inhibit interaction of CIB1 with αIIb subunit as well as Cib1-/- platelets to evaluate the consequence of CIB1 interaction with αIIb on outside-in signaling.
RESULTS: Fibrinogen binding to αIIbβ3 results in calcium-dependent interaction of CIB1 with αIIb, which is not required for filopodia formation. Dynamic rearrangement of cytoskeleton results in CIB1-dependent recruitment of FAK to the αIIb complex and its activation. Disruption of the association of CIB1 and αIIb by incorporation of αIIb peptide or anti-CIB1 inhibited both FAK association and activation. Furthermore, FAK recruitment to the integrin complex was required for c-Src activation. Inhibition of c-Src had no effect on CIB1 accumulation with the integrin at the filopodia, suggesting that c-Src activity is not required for the formation of CIB1-αIIb-FAK complex.
CONCLUSION: Our results suggest that interaction of CIB1 with αIIb is one of the early events occurring during outside-in signaling. Furthermore, CIB1 recruits FAK to the αIIbβ3 complex at the filopodia where FAK is activated, which in turn activates c-Src, resulting in propagation of outside-in signaling leading to platelet spreading.
Recommended Citation
Naik, Meghna U.; Naik, Tejal U.; Summer, Ross; and Naik, Ulhas P., "Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets." (2017). Department of Medicine Faculty Papers. Paper 208.
https://jdc.jefferson.edu/medfp/208
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
28542214
Comments
This article has been peer reviewed. It is the author’s final published version in PLoS ONE
Volume 12, Issue 5, May 2017, Article number e0176602.
The published version is available at DOI:10.1371/journal.pone.0176602. Copyright © Naik et al.