| First Author | Wang Y | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 14 | Pages | 2743-52 |
| PubMed ID | 23372168 | Mgi Jnum | J:196476 |
| Mgi Id | MGI:5488558 | Doi | 10.1182/blood-2012-07-445205 |
| Citation | Wang Y, et al. (2013) Platelets lacking PIP5KIgamma have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion. Blood 121(14):2743-52 |
| abstractText | Three isoforms of phosphatidylinositol-4-phosphate 5-kinase (PIP5KIalpha, PIP5KIbeta, and PIP5KIgamma) can each catalyze the final step in the synthesis of phosphatidylinositol-4,5-bisphosphate (PIP2), which in turn can be either converted to second messengers or bind directly to and thereby regulate proteins such as talin. A widely quoted model speculates that only p90, a longer splice form of platelet-specific PIP5KIgamma, but not the shorter p87 PIP5KIgamma, regulates the ligand-binding activity of integrins via talin. However, when we used mice genetically engineered to lack only p90 PIP5KIgamma, we found that p90 PIP5KIgamma is not critical for integrin activation or platelet adhesion on collagen. However, p90 PIP5KIgamma-null platelets do have impaired anchoring of their integrins to the underlying cytoskeleton. Platelets lacking both the p90 and p87 PIP5KIgamma isoforms had normal integrin activation and actin dynamics, but impaired anchoring of their integrins to the cytoskeleton. Most importantly, they formed weak shear-resistant adhesions ex vivo and unstable vascular occlusions in vivo. Together, our studies demonstrate that, although PIP5KIgamma is essential for normal platelet function, individual isoforms of PIP5KIgamma fulfill unique roles for the integrin-dependent integrity of the membrane cytoskeleton and for the stabilization of platelet adhesion. |
