The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization

Audrey Gérard; Alexander E E Mertens; Rob A van der Kammen; John G Collard

doi:10.1083/jcb.200608161

The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization

J Cell Biol. 2007 Mar 12;176(6):863-75. doi: 10.1083/jcb.200608161.

Authors

Audrey Gérard¹, Alexander E E Mertens, Rob A van der Kammen, John G Collard

Affiliation

¹ Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.

Abstract

Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish T cell polarity are poorly understood. We show that the activation of the partitioning defective (Par) polarity complex is a key event during Rap1- and chemokine-induced T cell polarization. Intracellular localization and activation of the Par complex are initiated by Rap1 and require Cdc42 activity. The Rac activator Tiam1 associates with both Rap1 and components of the Par complex, and thereby may function to connect the Par polarity complex to Rap1 and to regulate the Rac-mediated actin remodelling required for T cell polarization. Consistent with these findings, Tiam1-deficient T cells are impaired in Rap1- and chemokine-induced polarization and chemotaxis. Our studies implicate Tiam1 and the Par polarity complex in polarization of T cells, and provide a mechanism by which chemokines and Rap1 regulate T cell polarization and chemotaxis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins / analysis
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Polarity / physiology*
Chemokines / pharmacology*
Chemotaxis, Leukocyte*
Guanine Nucleotide Exchange Factors / metabolism
Humans
Hyaluronan Receptors / analysis
Hyaluronan Receptors / metabolism
Membrane Proteins / analysis
Membrane Proteins / metabolism
Protein Kinase C / analysis
Protein Kinase C / metabolism
T-Lymphocytes / cytology
T-Lymphocytes / immunology*
T-Lymphoma Invasion and Metastasis-inducing Protein 1
cdc42 GTP-Binding Protein / analysis
cdc42 GTP-Binding Protein / metabolism
rap1 GTP-Binding Proteins / metabolism*

Substances

Adaptor Proteins, Signal Transducing
CD44 protein, human
Cell Cycle Proteins
Chemokines
Guanine Nucleotide Exchange Factors
Hyaluronan Receptors
Membrane Proteins
PARD3 protein, human
T-Lymphoma Invasion and Metastasis-inducing Protein 1
TIAM1 protein, human
protein kinase C zeta
Protein Kinase C
cdc42 GTP-Binding Protein
rap1 GTP-Binding Proteins