TY - JOUR
T1 - Organization of the integrin LFA-1 in nanoclusters regulates its activity
AU - Cambi, Alessandra
AU - Joosten, Ben
AU - Koopman, Marjolein
AU - de Lange, Frank
AU - Beeren, Inge
AU - Torensma, Ruurd
AU - Fransen, Jack A
AU - Garcia-Parajó, Maria
AU - van Leeuwen, Frank N
AU - Figdor, Carl G
PY - 2006/10
Y1 - 2006/10
N2 - The beta2-integrin LFA-1 facilitates extravasation of monocytes (MOs) into the underlying tissues, where MOs can differentiate into dendritic cells (DCs). Although DCs express LFA-1, unlike MOs, they cannot bind to ICAM-1. We hypothesized that an altered integrin organization on the DC plasma membrane might cause this effect and investigated the relationship between membrane organization and function of LFA-1 on MOs and DCs. High-resolution mapping of LFA-1 surface distribution revealed that on MOs LFA-1 function is associated with a distribution in well-defined nanoclusters (100-150-nm diameter). Interestingly, a fraction of these nanoclusters contains primed LFA-1 molecules expressing the specific activation-dependent L16-epitope. Live imaging of MO-T-cell conjugates showed that only these primed nanoclusters are dynamically recruited to the cellular interface forming micrometer-sized assemblies engaged in ligand binding and linked to talin. We conclude that besides affinity regulation, LFA-1 function is controlled by at least three different avidity patterns: random distributed inactive molecules, well-defined ligand-independent proactive nanoclusters, and ligand-triggered micrometer-sized macroclusters.
AB - The beta2-integrin LFA-1 facilitates extravasation of monocytes (MOs) into the underlying tissues, where MOs can differentiate into dendritic cells (DCs). Although DCs express LFA-1, unlike MOs, they cannot bind to ICAM-1. We hypothesized that an altered integrin organization on the DC plasma membrane might cause this effect and investigated the relationship between membrane organization and function of LFA-1 on MOs and DCs. High-resolution mapping of LFA-1 surface distribution revealed that on MOs LFA-1 function is associated with a distribution in well-defined nanoclusters (100-150-nm diameter). Interestingly, a fraction of these nanoclusters contains primed LFA-1 molecules expressing the specific activation-dependent L16-epitope. Live imaging of MO-T-cell conjugates showed that only these primed nanoclusters are dynamically recruited to the cellular interface forming micrometer-sized assemblies engaged in ligand binding and linked to talin. We conclude that besides affinity regulation, LFA-1 function is controlled by at least three different avidity patterns: random distributed inactive molecules, well-defined ligand-independent proactive nanoclusters, and ligand-triggered micrometer-sized macroclusters.
KW - Cell Adhesion
KW - Cell Aggregation
KW - Cell Membrane/metabolism
KW - Dendritic Cells/physiology
KW - Humans
KW - Intercellular Adhesion Molecule-1/metabolism
KW - Lymphocyte Function-Associated Antigen-1/metabolism
KW - Membrane Microdomains/physiology
KW - Models, Biological
KW - Monocytes/physiology
KW - T-Lymphocytes/physiology
UR - http://www.scopus.com/inward/record.url?scp=33749476819&partnerID=8YFLogxK
U2 - 10.1091/mbc.e05-12-1098
DO - 10.1091/mbc.e05-12-1098
M3 - Article
C2 - 16855029
SN - 1059-1524
VL - 17
SP - 4270
EP - 4281
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 10
ER -