Regulation of Conformer-specific Activation of the Integrin LFA-1 by a Chemokine-triggered Rho Signaling Module

Overview

Journal Nat Immunol

Date 2009 Jan 13

PMID 19136961

Citations 73

Authors

Matteo Bolomini-Vittori

Alessio Montresor

Cinzia Giagulli

Donald Staunton

Barbara Rossi

Marianna Martinello

Gabriela Constantin

Carlo Laudanna

Affiliations

Soon will be listed here.

Abstract

Regulation of the affinity of the beta(2) integrin LFA-1 by chemokines is critical to lymphocyte trafficking, but the signaling mechanisms that control this process are not well understood. Here we investigated the signaling events controlling LFA-1 affinity triggering by chemokines in human primary T lymphocytes. We found that the small GTPase Rac1 mediated chemokine-induced LFA-1 affinity triggering and lymphocyte arrest in high endothelial venules. Unexpectedly, another Rho family member, Cdc42, negatively regulated LFA-1 activation. The Rho effectors PLD1 and PIP5KC were also critical to LFA-1 affinity modulation. Notably, PIP5KC was found to specifically control the transition of LFA-1 from an extended low-intermediate state to a high-affinity state, which correlated with lymphocyte arrest. Thus, chemokines control lymphocyte trafficking by triggering a Rho-dependent signaling cascade leading to conformer-specific modulation of LFA-1 affinity.

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