Abstract
Leukocyte adhesion requires β2-integrin activation. Resting integrins exist in a bent-closed conformation—i.e., not extended (E−) and not high affinity (H−)—unable to bind ligand. Fully activated E+H+ integrin binds intercellular adhesion molecules (ICAMs) expressed on the opposing cell in trans. E−H− transitions to E+H+ through E+H− or through E−H+, which binds to ICAMs on the same cell in cis. Spatial patterning of activated integrins is thought to be required for effective arrest, but no high-resolution cell surface localization maps of activated integrins exist. Here, we developed Super-STORM by combining super-resolution microscopy with molecular modeling to precisely localize activated integrin molecules and identify the molecular patterns of activated integrins on primary human neutrophils. At the time of neutrophil arrest, E−H+ integrins face each other to form oriented (non-random) nanoclusters. To address the mechanism causing this pattern, we blocked integrin binding to ICAMs in cis, which significantly relieved the face-to-face orientation.
Original language | English (US) |
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Pages (from-to) | 119-130.e5 |
Journal | Cell Reports |
Volume | 26 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2 2019 |
Externally published | Yes |
Keywords
- STORM
- TIRF
- human
- integrin
- integrin activation
- molecular modeling
- neutrophil
- superresolution
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology