Platelets lacking p90 PIP5KIγ have impaired anchoring of their cell membrane with the cytoskeleton. (A) Platelets were analyzed for their ability to form membrane tethers by an optical trap. The figure illustrates that pulling on the membrane-attached fibrinogen-coated bead will only stretch the membrane when membrane-bound integrins are not anchored to the underlying cytoskeleton. (B) The ability of PIP5KIγ E17^−/− PF4 Cre⁺ platelets to form membrane tethers is shown. Tethers were rarely seen in PIP5KIγ E17^−/− PF4 Cre⁻ control platelets. (C-D) PIP5KIγ E17^−/− CMV Cre⁺ and PIP5KIγ E17^−/− CMV Cre⁻ platelets were perfused over immobilized (C) collagen or (D) fibrinogen at a wall shear stress of 1 dyn/cm² for 10 minutes. After changing to platelet-free buffer, the wall shear stress was increased every 20 seconds up to 40 dyn/cm², and the platelet covered area was measured. The data in panels C and D represent the mean ± standard error of the mean of 5 experiments. *P < .05 relative to wild-type platelets at the same wall shear stress.