Transmission electron microscopy of erythrocyte membrane skeleton. Dematin FLKO erythrocytes are immature and have grossly deranged membrane skeletons. Comparison of the surface topology of (A) WT and (B) dematin FLKO erythrocytes. The structure of dematin FLKO erythrocytes is replete with invaginations that correspond to coated pits. (A) WT mature erythrocytes have a featureless surface. The skeleton underlying the membrane of dematin FLKO erythrocytes is abnormal, having many focal disruptions in the (D) spectrin-based skeleton compared with the (C) WT membrane skeleton. Bars correspond to 0.2 μm. Statistical analysis of the pore size was performed. Mann-Whitney test, 2-tailed, P < .0001. (E-F) Proposed model of dematin–membrane complex. Dematin and adducin coanchor the spectrin–actin complex to the erythrocyte plasma membrane. (E) Note that the mouse erythrocyte membrane does not contain any glucose transporter-1 (GLUT1), and therefore the receptor that links dematin to the membrane is not yet known. (F) Deletion of dematin causes rupture of the linkage between the spectrin–actin complex and the plasma membrane due to the secondary loss of adducin, resulting in concomitant decrease of both spectrin and actin at the junctional complex.