Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity

Alessandra Cambi, Ben Joosten, Marjolein Koopman, Frank de Lange, Inge Beeren, Ruurd Torensma, Jack A. Fransen, M.F. Garcia Parajo, Frank N. van Leeuwen, Carl Figdor

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Abstract

The β2-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
Original languageUndefined
Pages (from-to)4270-4281
JournalMolecular biology of the cell
Volume17
Issue number10
DOIs
Publication statusPublished - 2006

Keywords

  • IR-74144

Cite this

Cambi, A., Joosten, B., Koopman, M., de Lange, F., Beeren, I., Torensma, R., ... Figdor, C. (2006). Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity. Molecular biology of the cell, 17(10), 4270-4281. https://doi.org/10.1091%2Fmbc.E05-12-1098
Cambi, Alessandra ; Joosten, Ben ; Koopman, Marjolein ; de Lange, Frank ; Beeren, Inge ; Torensma, Ruurd ; Fransen, Jack A. ; Garcia Parajo, M.F. ; van Leeuwen, Frank N. ; Figdor, Carl. / Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity. In: Molecular biology of the cell. 2006 ; Vol. 17, No. 10. pp. 4270-4281.
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abstract = "The β2-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",
keywords = "IR-74144",
author = "Alessandra Cambi and Ben Joosten and Marjolein Koopman and {de Lange}, Frank and Inge Beeren and Ruurd Torensma and Fransen, {Jack A.} and {Garcia Parajo}, M.F. and {van Leeuwen}, {Frank N.} and Carl Figdor",
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Cambi, A, Joosten, B, Koopman, M, de Lange, F, Beeren, I, Torensma, R, Fransen, JA, Garcia Parajo, MF, van Leeuwen, FN & Figdor, C 2006, 'Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity' Molecular biology of the cell, vol. 17, no. 10, pp. 4270-4281. https://doi.org/10.1091%2Fmbc.E05-12-1098

Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity. / Cambi, Alessandra; Joosten, Ben; Koopman, Marjolein; de Lange, Frank; Beeren, Inge; Torensma, Ruurd; Fransen, Jack A.; Garcia Parajo, M.F.; van Leeuwen, Frank N.; Figdor, Carl.

In: Molecular biology of the cell, Vol. 17, No. 10, 2006, p. 4270-4281.

Research output: Contribution to journalArticleAcademic

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 Parajo, M.F.

AU - van Leeuwen, Frank N.

AU - Figdor, Carl

PY - 2006

Y1 - 2006

N2 - The β2-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 β2-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 - IR-74144

U2 - 10.1091%2Fmbc.E05-12-1098

DO - 10.1091%2Fmbc.E05-12-1098

M3 - Article

VL - 17

SP - 4270

EP - 4281

JO - Molecular biology of the cell

JF - Molecular biology of the cell

SN - 1059-1524

IS - 10

ER -

Cambi A, Joosten B, Koopman M, de Lange F, Beeren I, Torensma R et al. Organization of the Integrin LFA-1 in Nanoclusters Regulates Its Activity. Molecular biology of the cell. 2006;17(10):4270-4281. https://doi.org/10.1091%2Fmbc.E05-12-1098