| First Author | Naik MU | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 5 | Pages | e0176602 |
| PubMed ID | 28542214 | Mgi Jnum | J:246833 |
| Mgi Id | MGI:5917571 | Doi | 10.1371/journal.pone.0176602 |
| Citation | Naik MU, et al. (2017) Binding of CIB1 to the alphaIIb tail of alphaIIbbeta3 is required for FAK recruitment and activation in platelets. PLoS One 12(5):e0176602 |
| abstractText | BACKGROUND: It is believed that activation of c-Src bound to the integrin beta3 subunit initiates outside-in signaling. The involvement of alphaIIb in outside-in signaling is poorly understood. OBJECTIVES: We have previously shown that CIB1 specifically interacts with the cytoplasmic domain of alphaIIb and is required for alphaIIbbeta3 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 alphaIIb cytoplasmic domain peptide and CIB1-function blocking antibody to inhibit interaction of CIB1 with alphaIIb subunit as well as Cib1-/- platelets to evaluate the consequence of CIB1 interaction with alphaIIb on outside-in signaling. RESULTS: Fibrinogen binding to alphaIIbbeta3 results in calcium-dependent interaction of CIB1 with alphaIIb, which is not required for filopodia formation. Dynamic rearrangement of cytoskeleton results in CIB1-dependent recruitment of FAK to the alphaIIb complex and its activation. Disruption of the association of CIB1 and alphaIIb by incorporation of alphaIIb 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-alphaIIb-FAK complex. CONCLUSION: Our results suggest that interaction of CIB1 with alphaIIb is one of the early events occurring during outside-in signaling. Furthermore, CIB1 recruits FAK to the alphaIIbbeta3 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. |
