2019 Cell Reports.pdf
2019-03-04T18:48:52Z (GMT) by
Leukocyte adhesion requires b2-integrin activation.<br>Resting integrins exist in a bent-closed conformation—<br>i.e., not extended (E) and not high affinity<br>(H)—unable to bind ligand. Fully activated E+H+ integrin<br>binds intercellular adhesion molecules (ICAMs)<br>expressed on the opposing cell in trans. EH transitions<br>to E+H+ through E+H or through EH+, which<br>binds to ICAMs on the same cell in cis. Spatial<br>patterning of activated integrins is thought to be<br>required for effective arrest, but no high-resolution<br>cell surface localization maps of activated integrins<br>exist. Here, we developed Super-STORM by<br>combining super-resolution microscopy with molecular<br>modeling to precisely localize activated integrin<br>molecules and identify the molecular patterns of activated<br>integrins on primary human neutrophils. At the<br>time of neutrophil arrest, EH+ integrins face each<br>other to form oriented (non-random) nanoclusters.<br>To address the mechanism causing this pattern, we<br>blocked integrin binding to ICAMs in cis, which significantly<br>relieved the face-to-face orientation.