Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets.
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.We have previously shown that CIB1 specifically interacts with the cytoplasmic domain of αIIb and is required for αIIbβ3 outsi...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5443481?pdf=render |
| _version_ | 1818172115738689536 |
|---|---|
| author | Meghna U Naik Tejal U Naik Ross Summer Ulhas P Naik |
| author_facet | Meghna U Naik Tejal U Naik Ross Summer Ulhas P Naik |
| author_sort | Meghna U Naik |
| collection | DOAJ |
| description | 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.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.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.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.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. |
| first_indexed | 2024-12-11T19:07:29Z |
| format | Article |
| id | doaj.art-35e5720680174d428653e376e7396baf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T19:07:29Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-35e5720680174d428653e376e7396baf2022-12-22T00:53:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017660210.1371/journal.pone.0176602Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets.Meghna U NaikTejal U NaikRoss SummerUlhas P NaikIt 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.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.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.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.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.http://europepmc.org/articles/PMC5443481?pdf=render |
| spellingShingle | Meghna U Naik Tejal U Naik Ross Summer Ulhas P Naik Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. PLoS ONE |
| title | Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. |
| title_full | Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. |
| title_fullStr | Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. |
| title_full_unstemmed | Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. |
| title_short | Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets. |
| title_sort | binding of cib1 to the αiib tail of αiibβ3 is required for fak recruitment and activation in platelets |
| url | http://europepmc.org/articles/PMC5443481?pdf=render |
| work_keys_str_mv | AT meghnaunaik bindingofcib1totheaiibtailofaiibb3isrequiredforfakrecruitmentandactivationinplatelets AT tejalunaik bindingofcib1totheaiibtailofaiibb3isrequiredforfakrecruitmentandactivationinplatelets AT rosssummer bindingofcib1totheaiibtailofaiibb3isrequiredforfakrecruitmentandactivationinplatelets AT ulhaspnaik bindingofcib1totheaiibtailofaiibb3isrequiredforfakrecruitmentandactivationinplatelets |